Good day, and thank you for standing by. Welcome to the 2seventy bio Conference Call on ASH 23 data. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Liz Hickin, Head of Investor Relations. Please go ahead. Thank you, operator, and good morning, everyone. This morning, we are pleased to discuss the Abecma data presented at this year's American Society of Hematology Annual Meeting. The data were also disclosed in a press release that 2seventy bio and Bristol Myers Squibb jointly issued last night. The press release can be found in the Investors and Media section of the company's website at 2seventybio.com. As a reminder, today's discussion will include forward-looking statements related to 2seventy bio's current plans and expectations, which are subject to certain risks and uncertainties. These forward-looking statements include statements regarding our strategic plans, timelines and expectations with respect to the development, manufacture, or sales of Abecma, and statements regarding our financial condition, expectations and other future financial results. Statements about the efficacy and perceived therapeutic benefits of Abecma, the potential indications and market opportunities therefore, statements about the results of the PFS analysis and potential impact of such results, and the timing and review of additional studies and regulatory applications for Abecma, among others. Actual results may differ materially due to various risks, uncertainties and other factors, including those described in the Risk Factors section of our most recent Form 10-K, quarterly reports, and other SEC filings. These forward-looking statements represent our views as of this call and should not be relied upon as representing our views as of any subsequent date. You are cautioned not to place any undue reliance on these forward-looking statements, and except as required by law, we undertake no obligation to update or revise any forward-looking statements. On today's call, Nick Leschly will share some opening remarks, and then Anna Truppel-Hartmann, SVP of Clinical Development, will present data from the KarMMa-2 Cohort 2C study, as well as KarMMa-3, and Steve Bernstein will add some additional Abecma commentary. Chip Baird will then share some commercial updates for Abecma and close the call. We will then take your questions. And now, I would like to turn the call over to Nick. Thanks, Liz. Good morning, everyone, especially those joining from the West Coast. We know it's early, and most of you have likely had a busy weekend at ASH. For me, I always find this weekend and this conference to be a great reminder, not just for the why 2seventy bio is here, but also so many in the industry and specifically in oncology. That's, of course, to bring hope and time to patients and their families dealing with cancer. I know we'll be digesting the data presented this weekend for many weeks, but suffices to say it's incredibly energizing and encouraging to see so much advancement in the field. While we often focus on the brilliant researchers and clinicians behind these studies, I also want to acknowledge the brave patients and their families who take a leap of faith to participate in these clinical studies and really put their trust in all of us. We should never take that for granted. On the next slide, we've summarized the key questions and our views, as we know it is a busy meeting with much data to digest across many studies and companies. A few take homes from our perspective. First, I want to quickly highlight the KarMMa-2 Cohort 2C data because we think it's very encouraging, indicative of Abecma's potential future role in the early treatment paradigm. In this frontline population, we saw very high response rates and an impressive 77% CR rate. Importantly, the durability of response in these patients that have received lenalidomide maintenance reinforce our belief in the registration KarMMa-9 study in a similar population, which is now open and enrolling. Shifting to KarMMa-3, the OS data is top of mind, and frankly, the reason we are here this morning. So what does it show us? First is, that the data is exciting and validating for Abecma in the third line. Specifically with respect to OS, the data are, as expected, confounded by crossover, which is to say that patients who were in the standard care arm and then relapsed, were able to go on and receive Abecma. In addition, we saw some early deaths in Abecma arm. These were predominantly in patients who were randomized to Abecma but had progressive disease or were otherwise ineligible to receive Abecma by the time it was available. As both Steve and Anna will cover, this highlights the importance of bridging therapy, especially in the high-risk patient population. Zooming out, the take-home is that despite these factors, there was no difference in overall survival, which we all know is an important finding. We are very encouraged by the data and look forward to discussing in more detail at the upcoming ODAC meeting. Finally, we know that BMS is excited and pushing hard on all fronts, including the commercial side. Chip will cover the intense and ongoing efforts. We, of course, can only share so much on that front, so we encourage discussions with our colleagues and partners at BMS for more details on the Abecma efforts. Now that I've stolen all the thunder, I'd like to turn it over to Anna to dive deeper into the clinical data. Anna? Thank you very much, Nick. First, I would like to highlight the updated analysis of the KarMMa-2 Cohort 2C study, which included patients in PR, a suboptimal response after transplant. The median follow-up for this analysis was 39.3 months. On the swimmer's plot, it is demonstrated that with ide-cel treatment after transplant, responses deepened. All treated patients remained alive, and no new safety signals have been reported. The overall response rate was 87.1%, and the complete response rate, 77.4%. At 36 months, the duration of response was 80.9% and PFS was 76.8%. The study allows to optionally receive lenalidomide maintenance. Of the eight patients who received lenalidomide maintenance, indicated by the red box at the lower right of the swimmer's plot, six achieved a best response of CR or higher, and two of VGPR. All responses are ongoing, and none of the 8 patients progressed at this data cut. The safety profile is in line with the known lenalidomide safety profile. Turning to the next slide. With these exciting results in mind, I would like to emphasize that the updated data of KarMMa-2 Cohort 2C continue to support the KarMMa-9 study, which is an ongoing Phase III study investigating ide-cel in patients with newly diagnosed multiple myeloma with suboptimal response to transplant. Transplant is the standard of care in newly diagnosed transplant-eligible patients. However, a high unmet need of patients not achieving a CR post-transplant remains. KarMMa-9 will address a unique, newly diagnosed myeloma segment by adding on to transplant. Moving on to the next slide. It is with great pleasure to present the positive final PFS analysis of KarMMa-3, the first randomized Phase III study with CAR T in myeloma. On the next slide, you'll see the pre-specified final analysis for PFS. The primary endpoint in the study remains this highly significant PFS of ide-cel versus standard of care. We are excited that those data have been presented at ASH yesterday in San Diego. Coming to the study design. In KarMMa-3, patients with multiple myeloma had to be exposed to two to four prior lines of therapy, as well as each of the most commonly used classes of therapies: an immunomodulatory drug, a proteasome inhibitor, and daratumumab, and they had to be refractory to the last line of treatment. Eligible patients were randomized to receive either ide-cel or 1 out of the 5 standard care options, as determined by the investigator based on the pre-treatment history of the patient prior to randomization. As you will see in a minute, it is important to know that in the ide-cel arm, bridging therapy was optional and was given in 86% of patients, was limited to one cycle, and required a minimum of 14 days washout. In addition, 29 patients remained untreated in the ide-cel arm, versus only 6 in the standard of care arm. Most importantly, in the context of overall survival, this study design allowed patients on the standard of care arm to receive ide-cel upon progression. 66%, the majority of patients in the standard of care arm, elected this option to cross over and to receive ide-cel upon confirmed progression. Turning to slide 11, I would like to give a short overview of the baseline characteristics of the study population. 386 patients were randomized in a two to one rule. The baseline characteristics were well balanced between the arms. Not only were 100% of the patients triple-class exposed, but two-thirds of the patients were also triple-class refractory. 95% were daratumumab-refractory, over 60% having high-risk cytogenetics. Given the evolving treatment landscape, we are seeing patients exposed to an IMiD, PI, and daratumumab earlier and earlier in the course of treatment. Even though patients are only exposed to two to four prior lines, this represents a heavily pretreated multiple myeloma population with very limited effective treatment options. Coming to the primary endpoint of the study, progression-free survival. The final PFS analysis clearly shows that ide-cel continued to show a significantly longer median PFS of 13.8 months, compared to the standard regimen with a median PFS of 4.4 months. This represents a 51% reduction in risk of progression or death, consistent with the KarMMa-3 interim analysis. As mentioned before, effective treatment options in this triple-class exposed and refractory population are sparse, which is reflected in the results of the standard of care arm, and which clearly demonstrates the superiority of ide-cel in its first randomized CAR T trial in myeloma. In addition, with extended follow-up, the safety profile of ide-cel was consistent with prior reports, with no new safety signals identified. Of note, no GBS or Parkinsonism were reported. Turning to slide 13, to the secondary endpoints. The positive outcome in PFS is also reflected in a key secondary endpoint of overall response rates, which was significantly improved. The response was deepened with a complete response rate increase of 5% in the ide-cel arm and remained unchanged for standard regimens. As presented in another oral session, the health-related quality of life data collected in KarMMa-3 demonstrated that ide-cel continued to demonstrate durable, statistically significant, and clinically meaningful improvement in patient-reported outcomes. Turning to the next slide. For the first time, we were able to present an interim analysis of overall survival in KarMMa-3. As reflected in hazard ratio of 1.01, there was no difference between the ide-cel arm and the standard of care arm in overall survival. However, I would like to highlight three important factors that are confounding the interpretation of this analysis. First, as mentioned before, more than half of patients in the standard arm received ide-cel upon confirmed progression from the standard of care regimen. Since progression-free survival was short in the standard arm, most of those patients received ide-cel within 16 months and as early as three months after randomization. Forty-two percent have crossed over at month 15, as shown in the ITT Kaplan-Meier curve on the left. This crossover is a key confounding factor for the interpretation of the overall survival results. As you can see on the right side of the slide, a pre-specified analysis was conducted to adjust for this crossover and shows an overall survival benefit of ide-cel with a hazard ratio of 0.72. On the next slide, I would like to speak about the second confounding factor of this interim overall survival results. An imbalance was observed between treatment arms in the proportion of patients who died within 6 months from randomization, with 12% in the ide-cel arm and only 7% in the control arm. Of note, the majority of patients randomized to ide-cel who died within 6 months from randomization did not receive ide-cel. In both arms, this subgroup of patients who died within six months from randomization presented with a high percentage of high-risk baseline disease characteristics known to be associated with poor prognosis compared with their respective ITT population. No difference in death rates due to AEs were observed between the treatment arms. In summary, the early death in the first six months occurred most commonly in patients with multiple high-risk features, mostly due to the myeloma progression, and very importantly, in patients who never received ide-cel. Coming on the next slide to the third of the important confounding factors for overall survival, the bridging therapy given in the ide-cel arm. There was a lower use of effective bridging regimen in the ide-cel arm. DPd and Kd, the two regimens with the most reduction of disease burden, as shown at a presentation at IMS this year, were used less in the ide-cel arm compared to the use of those most effective regimens in the control arm, as highlighted by the red boxes. As a reminder, bridging therapy was optional, and 17% of patients did not receive bridging after apheresis. Also, bridging was limited to one cycle, and the median washout period was 24 days prior ide-cel infusion. In total, the median time without therapy within the first 60 days after randomization was much longer of 26 days in the ide-cel arm and only six days in the standard of care arm. Turning to the next slide, considering the two confounding factors of suboptimal bridging and the patients who died early in the ide-cel arm due to rapidly progressing disease, I would like to present the overall survival data in the treated population only. By removing patients who remained untreated in both arms, the overall survival trends in favor of ide-cel with a hazard ratio of 0.83, and this despite the crossover of patients from the standard of care arm to the ide-cel arm. In conclusion, KarMMa-3 demonstrates a significantly longer and clinically meaningful improvement of PFS with ide-cel versus standard regimen in this heavily pretreated but earlier line patient population. The patient-centric KarMMa-3 design allowed crossover, which confounds the OS interpretation. By adjusting for crossover in a pre-specified analysis, showed improved overall survival with ide-cel versus standard regimen. The bridging therapy was suboptimal for patients with multiple high-risk features and rapidly progressing disease, which highlights the importance of effective bridging therapy. KarMMa-3 shows a favorable benefit-risk profile with ide-cel and supports the use of ide-cel in patients with triple-class exposed earlier-line relapsed/refractory myeloma patients, which represents a population with poor survival outcomes with conventional therapy. Thank you very much for the opportunity of presenting this positive outcome of KarMMa-3, as well as our future plans with Abecma. I would like to now hand over to Steve. Thanks, Anna, and good morning, everybody. So let me take a moment to put all of this exciting data that was presented at ASH into perspective. So first, we discussed the excellent outcome seen for patients having an inadequate response to transplant when treated with Abecma in our KarMMa-2C study. As Anna mentioned, this data strongly supports newly diagnosed multiple myeloma. We're exploring the benefit of Abecma, followed by lenalidomide for patients having an inadequate response to transplant. Indeed, the fact that even with longer follow-up, there's still none of the eight patients that received lenalidomide maintenance after ide-cel in KarMMa-2C that progressed. And this further supports the underlying hypothesis that's being tested in KarMMa-9. Next, we discuss the KarMMa-3 data. As more and more patients are being exposed to triple class therapy earlier in their treatment course, such patients, upon progression, represent a large population of patients in desperate need of effective therapy, and indeed, it is in such patients that Abecma has shown to have a meaningful and significant improvement, not only in progression-free survival, but as was reported at ASH, in patient-reported quality of life outcomes compared to that of standard of care in our KarMMa-3 study. You've seen that the overall survival, which was a secondary endpoint in this study, was highly confounded only by the crossover, which was designed to provide patients that progressed on standard of care therapy an opportunity to receive Abecma that did not actually get treated with ide-cel. So indeed, what was so helpful in this was that our understanding that many of the latter patients had high-risk features associated with rapidly progressive disease and had inadequate bridging therapy, informs us that such high-risk patients need aggressive bridging so that they can go, go on to receive ide-cel. And finally, as patients meeting the strict criteria for entry into clinical trials are not always representative of the majority of patients that physicians see in their office, the fact that Abecma continues to demonstrate significant benefit in the real-world setting with consistent efficacy, consistent safety, despite being a much sicker patient population than seen in the pivotal KarMMa trial, is very clinically relevant. And with that, I'll turn it over to Chip. Thanks, Steve and Anna. Very exciting data. I'd like to close by highlighting what we and our partners at BMS are doing to support Abecma in the commercial setting. We believe Abecma is an important therapy in the treatment of multiple myeloma, and we're optimistic about a return to growth in 2024. We are pursuing a number of efforts to get Abecma back on track. First, we're increasing the number of U.S. treatment sites. We know that half the patients in the late-line setting are not receiving a CAR T or other innovative therapy, and that is partially due to access to treatment. We have significantly expanded the site footprint and will continue to do so in 2024. Second, we are educating on treatment sequencing. Emerging data is showing that patients who receive a CAR T before other BCMA target therapies do better overall. So that's an important message that we're emphasizing with physicians. Third, we are continuing to educate on Abecma's track record of reliable in-spec manufacturing and on the favorable safety profile. And the data from this year's ASH Meeting add to the efficacy profile, which shows that Abecma has an important role to play in the treatment of multiple myeloma. We look forward to building on this growing body of data in the KarMMa-9 study. With all of this, I want to acknowledge that there's still some uncertainty in what we'll see for Abecma in the next couple of quarters. We're confident in the plan that we and BMS have in place and are clearly energized by the clinical data we are seeing. So we have a lot of reasons to be optimistic about this product and are pleased that we have a great partner in BMS to put in the important work to get this product to patients. With that, we're happy to take your questions, and we'll turn it over to the operator. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Yaron Werber from TD Cowen. Great, thanks for taking my question. So I've maybe just a couple, when you're looking at. And this is relating to the survival data. When you're looking at the initial 6 months, I think you've done a nice job showing us exactly some of the elements that kind of led to almost what seems to be, you know, kind of an adverse trend. And then after, you know, 15 months or so, excuse me, it looks like patients do obviously, Abecma sort of benefit kicks in, and it looks like patients got inferior bridging therapy. Do you have a sense why that was the case? I mean, is it that t here's no evidence that the patients on Abecma sort of were more advanced and were deteriorating potentially faster. And then secondly, when you're again looking at the myeloma progression, it looked a little balanced, maybe a little bit more on ide-cel. I guess, putting it all together, I mean, there's obviously an AdCom coming up. What's the purpose of the AdCom, given this data? Yaron, thanks for the question here, and I, I think probably on the first one, as it speaks to the bridging, I think maybe Anna can jump in, but Steve, you know, feel free to trump me if you want to comment first. No, no, no. Go ahead, Nick. Anna, go for it. Thank you, Yaron, for the question. So as I highlighted before, the bridging, the patient population that were dying within the early six months between the two treatment arms were both highly enriched with high-risk features, and it was rapidly progressing disease. So this was not an imbalance between the two arms. However, what was the imbalance is the bridging therapies given. In the protocol, we had defined that only a maximum of one cycle of bridging therapy should be applied, and also we had a washout period that was also needed 14 days prior infusion. So and finally, it was optional to take a bridging therapy. So some patients did not receive bridging therapies at all and elected and some physicians elected not to treat with bridging. The other was really the washout period was prolonged in these 24 days median from stop of bridging until infusion. Finally, also the time, because there was only one cycle of bridging allowed, the time without therapy in the ide-cel arm was much longer than in the standard of care arm. All of this together led to the early deaths of the ide-cel patients, which was imbalanced compared to the standard of care arm, since there was a suboptimal treatment between apheresis and ide-cel, and the potential ide-cel infusion, which led to the majority of these early death patients to remain untreated. Thanks, Anna. The second question there, I wasn't 100% clear on, but maybe you can speak to, I think it was around basically, Yaron, you're saying, "Look, the data looks pretty good. I don't understand why, why do we need an ODAC?" Yaron, is that, is that fair to say, or is there a second question that I missed? Yeah, I mean, I think, you know, we were all obviously fairly concerned when an ODAC was called because of this potentially adverse Yeah. curve. But when you're looking at the totality of the data, is the FDA just want to air it publicly? Is that sort of before hopefully giving an approval, or, what, what else do you expect from that panel? So, Steve, I'll let you maybe jump in on that one, and then I'll close with a comment on it. Yeah, I mean, to be truthful, Yaron, as you can imagine, we really can't speak to why the FDA does want this Ad Com. We agree with you that the data speaks for itself. And because of that, and because when you look at the totality of the data and you assess what the benefit-risk ratio is for this, we're very confident that it'll be a positive Ad Com, but we can't speak to the reasons that the FDA is asking for this. Yeah, Yaron, so I'll say it here, since I'm not a clinician and I can't speak to the data, et cetera, I can say, you know, we don't agree with that decision to take it there, but at the same time, we understand that this is complex, right? We're sort of dealing with new territory in these randomized controlled study, in this setting, with where you have imbalances because of the nature of the treatment that Ana just walked through, right? With one starting right away, the control arm, and one having quite a bit of delay for a host of reasons. So how do you handle that? How do you handle an intent to treat kind of analysis that's not classical? So I think it is a precedent-setting, perhaps is more in the direction, but, our view is it's not based on the fundamentals of Abecma's value or its ability to sort of have some sort of, effect, a negative effect of some way. I think clearly we do not believe that. You can see that in the data here. That said, we got to respect what the agency is doing and the fact that they may want sort of a broader discussion on this because it is similar to what, hopefully in the future, will be many other treatments with these types of studies. So Yaron, that's probably as far as we can go, but hopefully you can hear that we and BMS feel quite confident. Next question, please. Thank you. One moment for our next question. Our next question comes from the line of Salveen Richter from Goldman Sachs. Thanks for taking our question. This is Tommy on for Salveen. This is a follow-up on the Ad Com question. Can you speak to your preparation here and how you intend to frame the OS data? And do you think that an additional trial might be required, given the OS data and some of your, the confounding effects that you spoke about? Thank you. This is Nick, and Steve, I'll pass it over to you here. I just want to qualify that we obviously cannot get into the details of that. I can say that we are intensely working with BMS, who are sort of doing the lion's share of this prep for sure, along with Ana and members of our team. So there's quite a bit of prep. We feel confident based on all the run-up to this, that we will be able to deliver what is a very, very strong story on behalf of Abecma that addresses the questions in and around overall survival. But that's a general statement there. I don't know, Steve, if you had anything else you could provide to Tommy. Yeah, I mean, I really. We obviously can't get into detail in terms of the interactions with the regulatory agents, but, as we really presented this data, this is data that now has been presented at ASH, and this is the data that you're seeing today. And we believe that, again, the data speaks for itself, that when you take the totality of the data for this patient population, that is a significant population with very poor outcomes, that the risk-benefit ratio, clearly to us, is in favor of Abecma. So, we respect the, we obviously respect the FDA wish to have the Ad Com, and we're confident, we feel confident that this data will speak for itself. This is Nick. Just one thing there, just to be clear, that we do not anticipate the need for another study, right? This is a conversation. You can see the data here and the benefit of Abecma. So, but let's sort of leave it at that, and then obviously, we'll have to get into the discussion with ODAC, and, and the folks there. The good news is that representation is, I think, a broad swath of clinical representation and so forth, and certainly so far, we've been getting a lot of very positive feedback at ASH and in and around that, is very supportive of Abecma and the data and what it's doing for the community and the patients. Thank you. Next question, please. Thank you. One moment for our next question. Our next question comes from the line of Daina Graybosch, from Leerink Partners. Hi, everyone. This is Rabib on for Daina. Acknowledging that it's very difficult to speak directly on the FDA's process and the ODAC, how is this overall survival result in KarMMa-3, you know, impacted the development strategy for Abecma itself going forward? As the manufacturing process improves, and the vein to vein time improves for Abecma, will this bridging therapy question be as important going forward? Thank you. Steve, if you want to be able to jump in on that one or Ana, I think the overall development strategy, I think, is unaffected, but please comment. Yeah, I mean, obviously in patients that have high-risk factors, by definition, their disease is often highly progressive. So we, we do think that bridging is still going to be an important part of the treatment schema for patients. I don't remember the other parts of the question. I'm sorry. So it was around how the OS result is going to impact the development strategy for Abecma going forward. And then the other one was about manufacturing as it relates to bridging therapy and improvements in such processes. Yeah, I mean, I don't see how, again, understanding now all of the caveats and the confounding of the overall survival, I don't see how that will affect further development of Abecma. We, you know, as we say, we're actually very pleased with the totality of the data. Chip, I don't know if you wanna handle the manufacturing question. Yeah, sure. Thanks, Steve. Yeah, I think, look, we've continued to make progress from the time this study was conducted to where we sit today commercially, which is less than 30 days on average for turnaround time from a manufacturing perspective, and that's important in these higher risk, more rapidly progressing patients. So I think continuing to be tight on the manufacturing side and then continuing to employ, and I think that this is one of the findings of the study, that bridging is important right up until the moment that the CAR is delivered to the patient. So both those things work together, and I think will inform how we think about the drug clinically and commercially. The other thing I just might add is, and this is where the KarMMa-2 C ohort 2C data, I think is quite relevant as it speaks to KarMMa-9 and our excitement as it relates to that, as that data is getting, you know, to very high response rates, very high CR rates in that sense, that I think bodes very well for Abecma continuing to participate and support the earlier populations as we go through it. So there is, I think, shared excitement with us and BMS in the community as we see that data, and being able to fill, as Anna said, a very specific niche there. And that's something that I think from a future perspective on Abecma, we're very excited about, and hence the significant investment across not only us, but also BMS. Next question, please. Thank you. At this time, I'm showing no further questions. I would now like to turn the conference back over to Nick Leschly for closing remarks. Thank you, and thank you, everybody, for most likely getting up quite early in a bigger context here. As you can hear, we're very excited about what we're up to in the context of Abecma now and contribute to the community, and also, I think I speak for BMS in that regard. So thank you for taking the time. If you have any specific or more detailed questions, please feel free to follow up with us directly. Thank you. Have a great day. This concludes today's conference call. Thank you for participating. You may now disconnect.