We're gonna get going here with our next company presenter at the BofA Annual Healthcare Conference. My name is Jason Gerberry. I'm one of the biotech analysts, and I'm pleased to be introducing our next company presenter, bluebird bio. We've got with us Andrew Obenshain, CEO, and Tom Klima, Chief Commercial Officer. Gentlemen, first off, thanks for joining us. Thank you. Thanks for having us. you know, bluebird bio is a company in effectively developing functional cures, routine therapies for complex and rare diseases. you know, you're now kind of at a point where you're pivoting from an R&D stage company to a commercial stage company. You've got two approved gene therapies, one on the way, filed for what you framed as probably your biggest market opportunity in sickle cell. maybe talk about the initial learnings from the rollouts of your two gene therapies for CALD and TDT and how the progress is going. Then we'll go into more specific questions from there. Great. Thank you. Thanks for having us, Jason. We are very pleased with the momentum of our launches so far. We have collected cells from 7 patients, thalassemia patients, 2 adrenoleukodystrophy patients. We've seen actually 3 of those collections happen in the 5-week stub period between our K and our Q. Really continuing to build momentum and very pleased with the adoption so far. This is important not only because of those launches as well, but also because we're setting the stage for the launch of lovo-cel. All the QTCs that we're setting up right now, we have 13 set up. All the QT-- and all the payer interactions we're having are setting the stage for a launch of lovo-cel, hopefully, with hearing from the FDA by the end of this year. Got it. Okay. Maybe it sounds like 2023 is very much a year of execution, setting up QTCs, improving your reach. Can you talk about sort of year one of launching, you know, gene therapies to the extent that there's sort of pent-up bolus for people who've been kind of hearing about these therapies and how that plays into, you know, early adoption versus. Should investors be thinking about these launches as more slow and steady ultimately? Go ahead, Tom. Sure. Yeah, happy to take that. As Andrew mentioned, we're really excited and pleased with the progress of our launches so far, for both ZYNTEGLO and SKYSONA, and really excited about setting the foundation for lovo-cel. We're thinking about the launch in terms of the uptake is more linear over time, and part of that is related to our setting up of the QTCs. If you remember back a few quarters ago, we were hyper-focused on getting our first 5 QTCs or our wave one QTCs or Qualified Treatment Centers on board. What we're seeing now is that those first 5 have all started treating a patient or more than 1 patient, and they're looking for additional patients. We're now, as Andrew mentioned, up to 13 treatment centers who can treat patients, and we're now seeing them start to initiate their first patient, you know, for either ZYNTEGLO or SKYSONA. Then we're actively in 30 additional QTCs right now with late-stage negotiations with contracting and everything. We expect them to be on board by the end of this year, where we'll have between 40 and 50 QTCs, and they'll start to bring patients on. It's, it's linear, but the momentum is clearly building. Yep. Is there something I assume fundamentally different about CALD versus TDT? You know, you do guide to new patient starts for CALD, perhaps a smaller patient population, maybe a little bit tighter network and easier to get a handle on sort of patients coming through the funnel. Whereas with TDT, maybe there are a lot more variables in terms of like QTC build out and sort of getting a handle on how the cell collections could evolve over the course of, say, first nine months of the year, which will be kind of like new starts that could translate to revenue in, say, 2023. Yeah. I think the biggest difference between CALD and why we feel comfortable with guiding to 5-10 patients is, number one, it's a small patient population, as you point out. Number two, it's a rapidly progressing disease. When these boys are identified, they're progressing rapidly, and they need to get treated as soon as possible. With TDT, there's a little bit more variable we're seeing. These patients are not acute. They're pretty accustomed to dealing with their red blood cell transfusions, there's less of an urgency there. That's a little bit, number one, a larger population, a little bit harder to predict. What we're seeing is that we're getting them in for their cell collection. We deliver back the drug product, but they're scheduling their treatment around life events, things like, you know, graduations, weddings, things like that. That's why we're not giving guidance yet. It's too early, and we'd like to see the consistency in a pattern before we give any guidance for TDT. Yep. Okay. From a process standpoint, you talk about a 70-90 day, sort of vein-to-vein time, effectively. You know, you're going through processes of getting, you know, reimbursement, collection of cells. Is that a good steady-state number to be thinking about? Is there any kind of variability up/down as you guys kind of get further out into the commercialization of your gene therapies? Yeah, I would say for now, the 70-90 days is pretty set, right? That's pretty common. That will be the same for all gene therapies at this time. Futuristically, hopefully, we can look to reduce and improve that time. Today, those are the testing and release assays that we agreed to with the FDA, and they just take some time. The manufacturing part of it's actually relatively short, but the testing takes a little bit of time. That's gonna be consistent for a while. The big update was obviously lovo-cel and getting the submission in. Maybe it seems like a no-brainer you'll get priority review, but, you know, just your level of confidence that you'll be able to get priority review with that? Well certainly that's always up to the FDA. We do have all the designations. We have the indication for it. We do believe that we will get that priority review. Yep. Can you just talk a little bit about sickle cell? You know, if you're able to kind of lay the foundation in 2023, how important is that for you to kind of hit the ground running if you've got an early 2024 approval? It'll be competitive. There'll be potentially another competitor with a gene therapy construct at the market around a similar time, presumably. Yeah. I think the biggest thing that everyone should understand is that we're actually launching today, as you mentioned. We're out there in our QTCs, Qualified Treatment Centers. We're setting up our network today. We are planning on getting to between 40 and 50 QTCs by the end of this year. All of the heavy lifting and the work to get a QTC up and running is being done this year. That means when we get the lovo-cel approval, should we get the lovo-cel approval, we can easily convert those ZYNTEGLO QTCs to lovo-cel QTCs. If you think about kind of the linear launch that we have with ZYNTEGLO today, if we can convert our QTCs to all lovo-cel QTCs, you could imagine all 40 or 50 of them potentially looking to be treating lovo-cel patients shortly after launch. The dynamic between Zynteglo and lovo-cel could be a lot different. From a competitive standpoint, you know, being out there first and building these relationships and actually treating patients today, gives us, I think, a huge competitive advantage. It's, you know, historically, I've talked about the market research we've done in the past. The actual experience and being out there doing it today is much more valuable. Got it. Okay. The regulatory process, I presume there's gonna be an AdCom. any specific elements of the label that you feel like are important one way or another in terms of being market limiting or giving you more latitude to operate in the space? We do anticipate that there will be an AdCom. Of course, that's up to the FDA. Sure. We are prepared for that. In fact, we've done 2 of them successfully in the past, I think we think we're pretty good at them. Yeah. We'd actually welcome that opportunity. in terms of the label, I, you know, I don't think there's any one particular area that the FDA would focus on. Overall, I think if we look back at our ZYNTEGLO AdComs, it was the efficacy and safety, which is pretty standard. I don't think there's any one element that they're gonna actually hone in on versus others. Mm-hmm. Okay. There's this, you know, obviously could be a much more substantial market size. If you can talk a little bit about of the 100,000 patients, right, you know, how you think about drilling down into what really is the TAM and, you know, you have patients who have more moderate to severe VOC, you know, as a symptom, and what proportion of patients ultimately kind of fall within that scope? Of the 100,000 patients roughly in the United States, with sickle cell disease, we believe that there are about 20,000 who have severe sickle cell disease or sickle cell with a history of VOEs, that also would be eligible for gene therapy. Of those 20,000, we've done a lot of market segmentation and looking at kind of a target patient at launch. I won't get too much into that, but we believe that about a third of the 20,000 are pretty excited for an innovative therapy like gene therapy. Maybe another third would require a little education and some experience from that first group of patients that will be treated. A third of the 20,000 will need some education over time. Mm-hmm. That's putting, you know, big level buckets, but we're really excited about the opportunity. Just to add to that anecdotally, as we're talking to our Qualified Treatment Centers today, they're talking about their patients that might be excited for ZYNTEGLO, but they're also talking about patients who have sickle cell disease that have been waiting for gene therapy. The third, right, that you think are, you know, most excited and, is there some characteristics that are common, be it maybe a high VOC burden, a risk of stroke, sorts of things that, like, would compel a patient to consider something like this versus, say, staying on oral therapies, hydroxyurea, Oxbryta, those types of agents? Yeah. I think it's a couple of things. I think it's a, you know, a group of patients that are probably between the age of 18 and 35, so they're in a transitional part of their life. They're maybe moving out from home, out from under the care of their mother, their parents, and really trying to take charge of their life and getting on to the next part of their life, whether that's school or work or whatever the case might be. Also they're already probably being seen by somebody who's caring for their sickle cell disease. It's probably not somebody who's not under care who just ends up in the emergency room once in a while. We've been, you know, active in the sickle cell market now for a decade, for over 10 years, so we feel that we understand this market, and we understand as we build out our QTCs, where we think the patients are gonna be most motivated to get treated. Got it. Any important sort of follow-up clinical data sets to expect over the course of the year from an investor standpoint, and just sort of, you know, rounding out the totality of the data sets that you have? We are continuing the HGB-210 trial, which is currently enrolling. We haven't actually given timelines in terms of publication there. Yeah. for that we are always very transparent with our data. We haven't actually announced any new publications, but there continue to be follow-up from our existing cohorts from HGB-206 and from beta thalassemia trials as well, and from HGB-210, and we'll kind of give more information over the course of the year when we start to release those. Yep. And just plans for moving into pediatrics. I think your competitor's running a 2-11 study and sort of how you're thinking about that. HGB-210 is a pediatric study as well, so we are enrolling that currently. We do have that pediatric study going. We were on clinical hold for pediatrics through December of this year, but we've reinitiated enrollment of pediatrics in that HGB-210 study. Yep. If you didn't have, the run-in period with Beta Thal- Mm-hmm. Is it fair to just assume you know, you'd be kind of a one-year lag in terms of just kind of building out the QTC network? Just trying to quantify, you know, what that advantage means versus, say, a competitor that is gonna be starting, you know, from approval and not having any QTCs online. Again, I think having the QTCs online and not only having them online, but having them with experience treating patients with gene therapy is gonna be a huge advantage. If you go back to our market research, you know, going back 5 years now, we've actually shown over time Target Product Profile of both our product, lovo-cel, and competitive products. What we've seen over time is The worst that we've seen is a 50/50 split just because they don't understand all of the data yet. We've actually also seen in previous years a huge advantage for lovo-cel, and they're really looking at the length of long-term follow-up that we have versus our competitor, the broader data set, the more robust data set. Mm-hmm. Also we hear that the LVV platform and the traceability of the LVV vector is important and is something that doctors are at least picking up on. We feel that again, the biggest competitive advantage we have is being out there today. We also think that clinically lovo-cel brings some things that gets patients and physicians pretty excited. Yep. Steady state though, I mean, I think in prior conversations, it sounds like most of the QTCs would offer both. I mean, maybe CAR T is the most apt analogy here in terms of, you know, offering different complex modalities, but just curious if that's a fair assessment. We're planning that most QTCs will offer both. I think most leading academic centers and cutting-edge, you know, centers that are treating rare diseases with gene therapies would wanna offer both. We have heard anecdotally that there are some that don't wanna go through the process twice, when they see very little difference in clinical benefit, between the two. I think you'll see some one-offs that offer only one therapy, but my guess is that most will offer both. Yep. You know, if you had to sort of the elevator pitch, what's gonna be the pitch? You know, why use this over exa-cel? I think it's gonna come down to the breadth and strength of the people that we have out in the field right now. They've been there and done it. We have some of the best cell and gene therapy experience in the field. They have relationships with the QTCs. They will continue to build those relationships through the ZYNTEGLO launch, which is going to really be advantageous for the lovo-cel launch. Again, I think if you look at the clinical profile, if you assume that it's basically the same, it comes down to little things like the long-term follow-up that you see with lovo-cel, the length of the data, the traceability of LV platform, and then also just our execution. Small, nimble company able to execute and deliver consistently. Yep. Can you just remind me what you've said historically about sickle pricing, just how you think about that? I'm mindful that there's a lot between now and that decision, but I think you've set beta-thal pricing. Your competitor will probably reference against that, it would seem like that's probably a reasonable reference point. Just can you just remind us on that front? Yeah. We know it's interesting. We're leading the way obviously with establishing value in these one-time curative therapies. We went through a rigorous process for both ZYNTEGLO and SKYSONA when we set those prices. We're going through the same process right now with lovo-cel for sickle cell disease. We'll consider, you know, the value that a one-time therapy brings for a, for a wildly underserved patient population. You know, look at many factors. Obviously the ICER draft report came out recently and we felt that that's one piece of the puzzle, but at least they're starting to recognize the value of one-time curative therapies and how they think about value and pricing. Stay tuned on that one. We'll talk more about it as we get closer to approval. Understood. Okay. Well- Yeah. Jason. Have any final parting remarks? No, just we're excited to keep these launches going, prepare for the launch of lovo-cel, and we look forward to updating you with continued progress throughout the course of the year. All right. Thank you, Jason. Well, best of luck. Thanks, Jason. Thank you. All right, guys. Thanks. Bye-bye. Bye.