Okay. Welcome to the 41st annual J.P. Morgan Healthcare Conference. My name is Matt Bannon, and I'm a healthcare banker here at JPM. I'm really excited to be setting the stage for our next presenting company, bluebird bio. Presenting on behalf of bluebird, we have CEO, Andrew Obenshain. Andrew, stage is yours. Good morning, everyone. To everyone here in the room and for later on the webcast, my name is Andrew Obenshain, I'm the CEO of bluebird bio. Thanks, Matt, and thanks, JP Morgan, for the opportunity to share the bluebird story as we kick off 2023, and which is poised to be a really significant year from both a regulatory and a commercial perspective, for bluebird bio. In today's presentation, and in the Q&A, we will be making forward-looking statements. I will refer you to our filings, with the SEC, to the statement which is in this presentation, which is on our website. Oops, wrong way. Many of you are familiar with bluebird's story. The last time we stood on this stage in 2000, then virtually in 2022, we were a gene therapy development company. Today you're gonna hear about bluebird, the gene therapy commercial company that is proving the commercial model for an entire field. I wanna begin by taking a look back. Bluebird has been a leader in the field of gene therapy for more than a decade. Gene therapy was science fiction when bluebird was founded, and now it is reality. We are bringing to life new treatment options that change the lives of patients and families. Starting with the column on the left, our technologies are proven and our experience is unparalleled. We've built our research on a decade of efforts and our experience in treating more than 180 patients across our programs. Moving to the middle, in 2022, that experience enabled bluebird bio to successfully navigate a biotech market meltdown, scrutiny of two of our leading products through FDA ad coms and ultimate approval, and the lift of a partial clinical hold. Along the way, we hit every single operational milestone that was in front of us. Today we have two of the five FDA-approved gene therapies, and we are on the cusp of filing our third, with the most significant growth opportunity yet, bringing a gene therapy to patients with sickle cell disease in the U.S. Many of my marks today will focus on the ongoing U.S. launches and preparations for bringing a therapy for sickle cell to the market. It's worth noting that we have wholly owned rights to all three of our programs globally. Shifting the focus to commercial impact. Combined, our programs have the opportunity to reach about 22,000 patients in the U.S. Specifically, in beta-thalassemia, we're reaching a sizable and underappreciated rare disease population with both significant unmet patient need and commercial opportunity. In 2023, that opportunity multiplies as we hope to bring gene therapy to a community that has long been underserved, the 20,000 patients in the U.S. living with severe sickle cell disease. This presentation is gonna focus for the most part on the two therapies for inherited hemoglobin disorders, ZYNTEGLO for beta-thalassemia, and lovo-cel for investigational, our investigational therapy for sickle cell. These are two unique therapies treating two unique diseases, but cared for by one set of physicians and one set of centers. Let's start with ZYNTEGLO, which was approved in August 2022 for the treatment of patients with beta-thalassemia requiring regular red blood cell transfusions. Importantly, this label has no age restrictions and no restrictions on genotype, and is approved now and available to patients commercially. The launch is off to a really strong start. Our commercial strategy is built upon three key pillars, which we believe are fundamental to the success of a gene therapy launch. First, like all therapies, patient engagement, education, and interest are key components of launch. With previously unseen efficacy and high unmet need, the demand for ZYNTEGLO is strong. Second, unique to ex vivo gene therapies, is the establishment of Qualified Treatment Centers. These transplant centers are where the cell collection and infusion takes place. These expert centers are both part of our supply chain, and they are ambassadors for our therapy. Finally, there's access and reimbursement. This is an area where we've also innovated. The pricing of one-time gene therapy is certainly not the same as pricing a chronic therapy. In the next few slides, I'd like to go into each one of these in more detail and to share with you the progress that we've made. As we go through this, I will also highlight how the progress we've made with ZYNTEGLO sets us up for the launch of lovo-cel. The same factors that are gonna make us successful with ZYNTEGLO will translate to lovo-cel. The path to treatment is multifaceted, and the patients come in. We learn about patients in a number of different ways. The first step of a patient raising their hand or in expressing interest is when they either contact our patient support program, my bluebird support, or they are referred in through a treatment center. And the earliest indicator of demand is that the patient initiates a benefit verification process to make sure that they're covered by insurance. Just four months into the launch, we have a total of 40 patients initiating benefit verification, which is an incredible indicator of the strong early demand for a rare disease. Next, there's signs of a stronger commitment to treatment. The reimbursement is confirmed through a more rigorous process of prior authorization, and that formal approval process is goes through an insurance. Then the patient is scheduled to have their cells collected. Now we're entering 2023 with multiple cell collections scheduled, and on average, it's taking only two weeks to get that prior authorization approved, which really speaks to two things. First, how the value, the fact that payers see value in this therapy. Second, it speaks to the quality of the team that we've had behind this access along the way. The last step in initiating therapy is actually the collection of the cells. I'm very happy to report that we announced this week at the conference that we've collected cells from our first ZYNTEGLO patient in the fourth quarter. The second core pillar of any ex vivo gene therapy launch is the treatment network or the Qualified Treatment Centers. These are highly specialized transplant centers where patients with beta-thalassemia are treated. We selected these centers based on the prevalence of beta thalassemia, and you can see that in the heat map circles on the slide. These are centers that are actively treating beta thalassemia patients today, but they're also centers that have experience with other cell therapies. We're making great progress in setting these up. We have, as planned, activated 10 QTCs, which are the red dots on this slide, and we're in the process of onboarding about 15 more who are either in about the contract negotiation phase. We are well on our way to having a network of 40- 50 QTCs by the end of the year. As you'll see later in the presentation, our QTC footprint is designed not only to maximize the launch of ZYNTEGLO, it also sets us up for a seamless transition to activate the QTC network for sickle cell disease later this year. The third pillar is focused on access and reimbursement. beta thalassemia is a serious, burdensome, life-threatening, and costly disease. We have a groundbreaking approach to medicine and a price of $2.8 million for ZYNTEGLO. We have offered payers an innovative payment strategy to mitigate the one-time cost of therapy. Payment is 100% upfront, but we offer up to an 80% rebate if the patient does not achieve transfusion independence within two years. In our phase III trial, 90% of our patients achieve transfusion or almost 90% of our patients achieve transfusion independence, and 100% of them, all of them who achieve transfusion independence, maintain transfusion independence. Just like patients and providers, payers believe in our therapy, and here are a few numbers that put that positive response in, forward. In just four months, we have $190 million lives covered. We have three PBMs who have signed outcome agreements. These are three of the largest PBMs in the U.S., and we have had zero ultimate denials. This is a truly remarkable payer update at this early in the launch, and most importantly, it means that patients are getting timely and quality access to ZYNTEGLO. We are confident in patient interest, and we're extremely encouraged by patient access. In our launch year, a key indicator of performance will be these patient starts. To put those in context, once a patient starts, there's a process Or cells are collected, there's a process that kicks off and leads from cell collection to infusion. Each drug product is unique to the patient. It is manufactured for that patient, and it takes about 70, 90 days to manufacture, test, release, and deliver that therapy back to the hospital. Therefore, bluebird bio currently recognizes revenue upon infusion, and we believe that we'll recognize that first revenue in Q1 of this year. I've talked about the significant opportunity we have in beta-thalassemia and how we are the first to bring a gene therapy to patients with inherited hemoglobin disorder. Not only is ZYNTEGLO an important standalone opportunity, it's also foundational for our future. The efforts we're making with ZYNTEGLO today and the successes that we're having in the market today will directly translate into the launch for lovo-cel disease. That will happen in three key ways. We'll be addressing the same treating physicians. We will be using the same QTC network. In fact, just a little aside here, on that contract, the last page of the ZYNTEGLO contract is a blank sheet for addendum to add lovo-cel upon approval. This means that we're doing the work now to set up the lovo-cel QTCs for later. Finally, all the relationships we have with the payers right now are going to be leverage for lovo-cel as well. Now, with sickle cell, we see an opportunity to address a critical unmet need for the 20,000 individuals living with sickle cell disease in the U.S. I just wanna talk about sickle cell disease for a second. It is a large patient population. Fully one in 365 Black babies born in the U.S. every single year are born with sickle cell disease. There is a significant unmet medical need. I think the hallmark of this disease is pain, but on the surface, these patients appear normal. Underneath, there is a significant organ damage. one in four patients have a stroke by the age of 45, and there's widespread risk of organ failure. If you look at the cost to the patient, 65% of those patients report giving up a job due to sickle cell disease. If you look at the cost to the system, it costs the system on average $4 million in direct medical costs, despite the fact that the median age of death is only 45. We are sorry. bluebird is proud to be advancing lovo-cel to potentially help this terrible, terribly underserved population. The impressive clinical data that has been reported multiple times in New England Journal of Medicine and at sequential ASH meetings. Our clinical data reflects the most robust data available with the longest follow-up across any gene therapy program for sickle cell disease. Earlier this week, we confirmed that we've completed the analytical comparability studies for the CMC portion of our FDA submission, and we are on track to submit our BLA for lovo-cel for the treatment of sickle cell disease in patients 12 years and over in the first quarter of this year. Concurrent with that regulatory process, we are building the infrastructure needed for the lovo-cel launch today and expanding our QTC network in anticipation of lovo-cel approval by year-end. You can see on this heat map the significant overlap in the most prevalent thalassemia and sickle cell populations in the U.S., indicating where we will be focusing our efforts and how beta thalassemia and sickle cell will overlap. In addition to the beta thalassemia prevalence, the planned expansion to 40- 50 QTCs by year-end 2023 prioritizes the proximity to sickle cell patients, ensuring that we place centers where those patients live. 65% of the sickle cell population will be within 50 mi of a QTC by the end of this year, 95% will be within 200 mi by the end of this year. We will continue to expand this QTC network in 2024 and beyond. Last but not least, I wanna talk about Skysona, which is a therapy that has been the soul of bluebird since its founding. Skysona is indicated for the treatment of cerebral adrenoleukodystrophy, which is a progressive neurodegenerative disease that primarily affects young boys and causes irreversible, devastating neurological decline. These boys are diagnosed early in the first decade of life. They lose the ability to talk. They lose the ability to eat. They lose the ability to see. They lose the ability to move, first go into a wheelchair, and then losing all mobility altogether. If left untreated, fully half of these boys will die by the time, at five years after diagnosis. We're very excited at bluebird bio to be setting up the infrastructure to bring Skysona to these patients in the U.S. We've activated two QTCs, we have three additional ones planned. Far, we have zero ultimate denials from payers, as the payers recognized the value and the urgency to treat. We believe that we will do about five to 10 patient starts in 2023, therefore helping between five to 10 boys and their families. Now, let's wrap up by taking a look at our financial position and our anticipated milestones over the course of next year. After a year of cost restructuring and substantial doubt about the financial future of bluebird bio, we are very pleased to report that we now have cash into the first quarter of 2024 and are on a much stronger financial footing, following almost $200 million in non-dilutive funding from the sale of our two PRVs. Retiring this near-term risk has been crucial as we execute on important milestones this year, including the 2 ongoing commercial launches and the submission and potential approval of lovo-cel expected at the end of 2023. We remain opportunistic in looking for ways to extend that cash runway beyond 2024. Speaking of milestones, we have a busy year ahead of us. 2023 is a year that where the rubber meets the road on the first commercial gene therapy launches, and bluebird bio is leading the race with two ongoing launches and our first to market position in inherited hemoglobin disorders. On the commercial side, we expect first commercial revenue in the first quarter of 2023 and a QTC expansion throughout the year, again, ending with 40-50 QTCs by the end of the year. For lovo-cel, we will submit the BLA in the first quarter of 2023 with a potential approval expected by year-end and a commercial launch in early 2024. bluebird bio has continued to set the standard for gene therapy. We started by setting that in the clinical and regulatory areas. Now we're setting that standard in the commercial areas. We're building momentum with near term commercial launches. We're very happy to be finally delivering our therapies to patients and their families in the U.S. market. With that, I will conclude. I'd like to invite Tom Klima up to the stage for Q&A. Thank you, everyone. All right. Just like to remind folks that you can submit a question through the Q&A portal if you're on the webcast, and I'll ask them on your behalf. First question, have you disclosed the price of Skysona? Yes. We disclosed the price, for both ZYNTEGLO and Skysona. The price of Skysona is $3 million. Got it. We can also take questions from the audience. There's a mic runner, so just raise your hand and we'll get that over to you. Andrew, how are you thinking about the competitive landscape and the potential impact of launching at the same time as your competitor? I first of all, I think it's been rather unique that we've had so many therapies come forward for sickle cell disease in the last several years, which is only good for the patients, for the patients. Of course, we're focused on making sure that we do the right thing with the launch of ZYNTEGLO, which we see as our first launch, and setting up that launch for lovo-cel, which we think puts us at a great advantage versus our competitor for the launch of lovo-cel. Maybe I'll turn it to Tom to talk a little bit about the competitive dynamics as well. Yeah, sure. The first thing that Andrew said is absolutely true. Patients with sickle cell disease have lived for a long time without significant innovation. We feel strongly that more therapies and more options available for patients only will improve patient care. As Andrew pointed out in his presentation multiple times, we are focused on execution right now, specifically on making sure that we get to the 40- 50 QTCs by the end of this year, and specifically that we work on value demonstration for lovo-cel as we did with ZYNTEGLO and Skysona. As we look at some of the market research that we've done over the years, we see a slight preference for lovo-cel consistently. That's based on our long-term follow-up and also based on the strength and traceability of the LVV platform. We remain confident in the launch of lovo-cel and remain dedicated, you know, committed to focus on execution right now. Got it. Right here. There's a mic on the way, but if you say it, I'll just repeat it. The other thing the patient when it comes to there's no kind of no or negative response from the patient. In that case, how do you follow up the case? Do you ask the patient to report after two years or payers do it? That's my first question. I can answer that. There is a regular follow-up schedule post-transplant, where the patient comes back to the Qualified Treatment Centers for follow-up visits, and it's measured then and reported to the payer. The Qualified Treatment Center directly report to the company? We have a registry. We have both a follow-up and a registry, and so it gets reported to the registry, which we then have access to as a company, and the payer can get that information as well. Follow-up? Go ahead. Yeah. My follow-up question is, in the case, maybe the patients have already paid some out-of-pocket money, and then when it comes to the day they are kind of compensated after two years, there's no response, then how do you pay back to the payer and the patient? The way to think about this is that, number one, just to recap on the outcomes-based agreement, we believe about 50% of our patients will be treated under an outcomes-based agreement. The outcomes-based agreement was really a tool or a mechanism to help us achieve both rapid access but also access, consistent with our label and clinical trials. We feel that that was a, you know, great accomplishment for us to achieve access so quickly, and very consistent with our clinical trials and label. The first thing to remind you is that in the clinical trials, 90% of patients achieved transfusion independence, and of those patients that achieved transfusion independence, 100% maintained it. We wouldn't expect, you know, rebates for patients not hitting transfusion independence to be very large. The rebate of up to 80% gets paid back to the payer. As far as you asked a different question about out-of-pocket expenses for a patient, keep in mind that this is a hospital inpatient treatment, and so out-of-pocket expenses don't really apply for an inpatient treatment. Thank you. Does the cash guidance you provided, does that include ramping up to 40-45 QTCs? Yes. The cash guidance we gave does include ramping up to the 40-50 QTCs. Got it. Thanks. T he 40 patients who have initiated BV, what percentage of those do you expect to convert? Go ahead, Tom. Yes. The 40 patients that we reported that are in the BV process, we reported that as because we believe that is a strong indicator of demand. It's way too early to try and predict how many of those 40 patients will move through the process all the way to treatment. It's encouraging that not only do we have 40 patients that have started the process with the BV, but many of those patients have also moved to the prior authorization phase, and we've seen no ultimate denials right now. We're seeing in the numbers that were reported strong demand up front and then consistency and confidence in reimbursement with the prior authorization process. Got it. Any questions from the audience? With other SCD launches, we've seen challenges, what ultimately gives you confidence in lovo-cel? First of all, this is a gene therapy launch, which is, I think, very different to some of the other launches we've seen to date. I think we have published some incredibly impressive efficacy, just transformative efficacy for these patients, which puts us in a very different, I think, position than some of those other launches. We certainly appreciate that the dynamics of this patient population are unique, and we're preparing ourselves for that. I would remind you that this launch of ZYNTEGLO is actually setting us up for the launch of sickle cell as well. Same QTCs, same physicians. Same payers. The progress that we can make this year in terms of setting up that infrastructure is really gonna help us with that launch of lovo-cel as well. Maybe I'll turn it to Tom to give any other color. Well said. I think the only thing I would add is it's hard to look at a proxy or look at another analog in this case in trying to determine where not only the opportunity is, but what the launch might look like. I feel that the best analog will be our own launch for ZYNTEGLO and our ability to get to 40- 50 QTCs and the patient starts that we can achieve with ZYNTEGLO. That will prove that the gene therapy the gene therapy model is here and hopefully gonna also apply in sickle cell disease. Got it. Go ahead. Two questions. What's on your sickle cell, what is the price of that and what's the price of the QTC? Question on price of sickle cell therapy and price of QTC. We have not priced sickle cell yet. We've priced ZYNTEGLO and Skysona. That will be later. In terms of the price of the QTC, I'm not sure if I understand the question. You can get 50 of them. You pay rent to an academic center. Of course. Oh, I see. Actually, Tom, do you want to? Sure. The way to think about a price of setting up a QTC is it's mostly headcount. We have a field force out there working with the QTCs as well as an internal operational team, as well as, you know, lawyers and everyone that goes along with it. There's no actual cost out of pocket to set up a QTC. It's just a headcount growth. Yeah. The QTC, I should explain, is the transplant center, usually in an academic hospital, that we are, we do a quality agreement with and a contract with, so that it is an existing infrastructure that we are contracting with. There's a question here. Looks like they just wanna know how you're thinking about the SCD market in terms of like a TAM, and of the spectrum of SCD patients, which ones do you think will opt for a gene therapy? Go ahead, Tom. We've done a lot of work with the sickle cell community, and in fact we've been involved with the sickle cell community as a company for 10 years now. We've done consistent market research for the last four or five years and feel that, as I said before, the sickle cell community's been dramatically underserved. These patients have lived without innovation and been shuffled around in some cases through the healthcare system. We also believe that there's a good number of sickle cell patients who are excited about a one-time potentially curative therapy. They're tired of living with their pain and being in and out of the hospital and excited about gene therapy. The way that we think about the roughly 20,000 patients who live with severe sickle cell disease is about a third of those patients are pretty excited for an alternative like gene therapy. A third of patients roughly might need a little more time and some additional education or other patient experiences to lean on. A third, gene therapy may not be for them, at least right now. We feel really confident in the patient demand, and we feel confident in delivering for patients. Got it. I've got a question here. Now that you've figured out the kinda distribution system, the payment system for hematology-related gene therapies, do you foresee eventually you might kind of license in other type of products in the area and distribute it to, you know, make more revenue? The team right now is focused on these three therapies in the U.S., and that's gonna be our focus for the coming years. Not only to bring these three therapies to the U.S., but the next dollars of investment will go towards improving those therapies, expanding indications, for example, pediatrics, in sickle cell disease. We do have a lot of expertise within bluebird bio, a lot of expertise within cell processing, a lot of expertise in going through the FDA with a complicated CMC product, a lot of expertise on the research side, as well. We certainly have an asset at bluebird bio that we envision in the future that we could use as a chassis to put other things on it through either internal development or through licensing and acquisition, but that's a much later project. For the next couple of years, it is a pure focus on launching these three therapies in the U.S. John? Just two questions. Just on the revenue, I would imagine you're gonna book 100% of the revenue in the first quarter when you do infuse the first patient. Is that the right way to think of it? Yeah. We would. The way the kinda cash flow works or the revenue works is we send an invoice when the bag is sent to the center. We recognize revenue on infusion. There'll be a reserve that we will hold back based on an anticipated amount that we would have to pay back in rebates. Got it. The last question, just the PRV market seems to be relatively stable. You guys have been active. Yeah. I'm just curious on any comments you'd have in regards to that market. Yeah, the PRV. Yeah. PRV. Yeah, priority review market. Yep, there's I think there's roughly about 17 PRVs that are out there right now, about 6 sell a year. It continues to be an active market. We saw an opportunity to monetize two of them relatively quickly, and in a high cost of capital environment, we thought that was prudent to take the cash now. Just on ZYNTEGLO, when can we expect guidance on the launch? Guidance in terms of what I would tell people to pay attention to is patient starts, because almost all patient starts will lead to revenue. We won't be guiding on revenue in the near future. We will be giving indicators of demand, and I think that we really paying attention to those patient starts. The dynamics of every launch, right? It's always tempting for a biotech company to try to predict them and to give early guidance, and I think a lot of biotech companies have been burned by that. We remain very confident in the launch. We've given some early metrics. We will continue to give some of those launch metrics as well. When the time is right, we will guide to most likely patient starts versus revenue. Got it. One final question from me. What is the future for bluebird? Just stepping back high level. You're clear about your near-term opportunities with two approved therapies and with SCD coming this year, how are you thinking about the long-term strategy for bluebird? I think I partially answered that already, but if you. We have three therapies, wholly owned global rights. We are focused on the U.S. only for those therapies right now for the next couple of years. We have a tremendous amount of opportunity both for in terms of making a patient impact and making an investor impact just with those three therapies in the U.S. That has been and will be our focus for the next couple of years. Beyond that, we do have the, as I mentioned, capabilities as a company to expand beyond those three therapies, and we have the. And then we also have the geographic expansion that will come in a future state. For the next two years, you will hear bluebird bio ad nauseam talk about the U.S. and these three therapies. Got it. Final questions from the audience? No. Thanks so much, Andrew and Tom, and the bluebird team. Bye. Thank you. Have a great rest of your conference. Thank you. Thanks, Matt.