Good day, and welcome to the SKYSONA launch call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there'll be a question and answer session. As a reminder, this call may be recorded. I would now like to turn the call over to Courtney O'Leary, Investor Relations. You may begin. Good morning everyone, and thank you for joining today's presentation. My name is Courtney O'Leary, Senior Manager of Investor Relations at bluebird bio. Before we begin, let me review our safe harbor statement. Today's discussions contain statements that are forward-looking under the Private Securities Litigation Reform Act of 1995, including statements of the company's plans, expectations, and intentions regarding our commercialization plans following the FDA approval of SKYSONA. Such statements are based on current expectations and assumptions that are subject to risks and uncertainties and involve a number of risk factors that could cause actual results to differ materially from projected results. A description of these risks is contained in our filings with the SEC, which are available on the Investor Relations section of our website, www.bluebirdbio.com. Today's agenda is as follows: Andrew Obenshain, our CEO, is going to provide some brief remarks on SKYSONA's approval and targeted commercial launch, and then we'll be joined by Tom Klima, Chief Commercial and Operating Officer, Rich Colvin, Chief Medical Officer, and Jason Cole, Chief Strategy and Financial Officer for Q&A. With that, I will turn the call over to Andrew. Thanks, Courtney, and good morning, everyone. Friday's approval of SKYSONA was a landmark moment for both the ALD community and for bluebird. For the ALD community, this long-awaited approval offers significant hope with the availability of a new option to slow the irreversible and devastating neurologic decline associated with the cerebral form of adrenoleukodystrophy or CALD. For bluebird, it marks our second FDA approval in a matter of weeks and cements our leadership in the field with two of the four FDA-approved gene therapies. CALD is more than just business for bluebird. It's personal. bluebird as a company was founded in 2010 to develop a new treatment for CALD, and children with this disease and their families have been at the heart of our mission ever since. To have reached this moment after a decade of research and development with many setbacks along the way is truly remarkable. SKYSONA received accelerated approval for the treatment of early active CALD in boys ages 4- 17 and is the first FDA-approved therapy shown to slow the progression of neurologic dysfunction for this devastating and fatal disease. CALD is ultra-rare, and it strikes otherwise healthy young boys in the prime of their development, typically between the ages of 4 and 7 years. In plain terms, without treatment over time, these boys progressively lose the ability to walk, to see, to use the toilet, to feed themselves, all while their families watch helplessly. Nearly half of the children who do not receive treatment die within 5 years. SKYSONA is an urgently needed treatment option. SKYSONA has been studied in the clinic through both our phase 2/3 study, ALD-102, and our phase 3 study, ALD-104, with a total of 67 patients treated. Patients treated with SKYSONA were assessed using the Neurologic Function Score and monitored for the emergence of 6 major functional disabilities associated with CALD progression, including loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement. You can only imagine how profoundly this impacts children and their families. The accelerated approval is based on a 24-month improvement in major functional disabilities free survival. The label includes a boxed warning on SKYSONA for hematologic malignancy. As previously reported, 3 boys treated in our clinical trials developed myelodysplastic syndrome, which is believed to be caused by insertion of the Lenti-D vector. As a reminder, at the conclusion of the FDA Advisory Committee meeting for SKYSONA in June, parents, clinicians, and all 15 members of the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee expressed their belief that SKYSONA is a valuable treatment option for appropriate patients despite this risk. We are confident that the risks of SKYSONA will be weighed carefully with the risks of other treatment approaches and of CALD itself as families and clinicians make these complex and deeply personal treatment decisions. Under accelerated approval, bluebird bio has agreed to provide confirmatory data to the FDA. We anticipate that the post-marketing requirement will be satisfied with data from patients already enrolled in our long-term follow-up study, LTF-304, which follows patients treated in our clinical trials for 15 years and from commercially treated patients. Additionally, concurrent with the completion of this review of the SKYSONA BLA, the FDA lifted the clinical hold put in place in August 2021. ALD is an extremely rare disease, and our commercial approach for SKYSONA will be tailored to this ultra-rare population. More specifically, ALD is estimated to affect approximately 1 in 21,000 newborn males in the U.S. Of those, approximately 4 in 10 are expected to develop the cerebral form of adrenoleukodystrophy. This results in an incidence of about 40 boys per year in the United States. We are focused on three key areas. A targeted qualified treatment center or QTC network, access and reimbursement, and patient support. Our QTCs include Boston Children's Hospital and Children's Hospital of Philadelphia, and we anticipate bringing a small number of additional established CALD treatment centers online by the end of this year and making commercial product available by Q4. The price of SKYSONA is $3 million, reflecting the clinical benefit it provides as an urgently needed treatment option to slow the progression of neurologic dysfunction in children impacted by progressive, irreversible, and fatal rare disease. We are confident that payers recognize the significance of SKYSONA as the first FDA-approved therapy for this disease, and we are committed to working with them to ensure patient access. Unlike ZYNTEGLO, bluebird bio does not intend to offer outcomes-based agreements for SKYSONA, as the rarity and complexity will make this extremely challenging to implement for both bluebird bio and payers. Importantly, we will be with patients every step of the way, and have built my bluebird support, our comprehensive program staffed by patient navigators that will support patients through all stages of the gene therapy journey, from when they express initial interest to connecting them with the QTC, benefits verification, and financial services for eligible patients. The last few months have been a major turning point for bluebird bio, with successful unanimous AdCom meetings for our first-in-class gene therapies, two FDA approvals, and a clear path to financial sustainability. With Friday's approval of SKYSONA, we have now secured our second priority review voucher, and we plan to promptly monetize and maximize the value of both in the near future. Our team is laser-focused on execution, and I'm excited to say that we've hit all of our operational milestones to date this year. As we transition to a commercial company, launch our first two gene therapies in the U.S., and finalize our BLA submission for sickle cell disease in Q1 2023, we remain steadfast in our commitment to execution and to ensuring that our business is as strong as our science. Before we transition to Q&A, I wanna thank every individual who's involved in the development of SKYSONA and convey my immense gratitude to the investigators and patients and their families who had the bravery to participate in our clinical trials and help bring us to this point. This has been a community effort. From the mothers who pushed for the first patients to be treated, to the physicians that cared for these boys and their families. We've been honored to stand alongside you as we together persist for purpose, and that purpose has been realized today. Thank you. With that, I will open up the call for Q&A. Operator? As a reminder, to ask a question, please press star one one. Our first question comes from Jason Gerberry of Bank of America. Your line is open. Hey, good morning, guys, and congrats on the approval. Two questions from me. First, on the market opportunity and helping us think about modeling this market in lieu of the label. Y ou have to treat patients per the label early in active CALD, so is that typically first year of diagnosis, year two, three? Just wondering if we should be thinking of more of a rolling incident type of population here and how you'd characterize that. Then my second question, when you had the TDT approval, you talked about some metrics for patients that might be interested and motivated to undergo TDT gene therapy. You know, given the progressive nature of CALD, I imagine that perhaps that motivation level is higher. If you could maybe just put some, I don't know, if you can characterize that dynamic a little bit, that'd be helpful. Thanks. Good morning, Jason. I'll pass that over to Tom, our Chief Commercial Officer, to respond. Yeah, sure. Good morning, Jason. The two points, I'll start with the second one first, and you're thinking about it spot on. With CALD, these boys and their families are urgently seeking treatment and treatment options, and so they're actively looking for QTCs and looking for all treatment options available. It's a different dynamic than what you would see with TDT. As Andrew mentioned, the incidence each year is 40 patients in the United States, and we are not changing our model based on the label or the accelerated approval. Obviously this is a smaller patient population that's urgently seeking treatment. Just to clarify on that then, once a patient's in their second or third year, they're not likely candidates for gene therapy post-diagnosis? Yeah. Jason, yeah, exactly. They progress very quickly, right? Think of this as an incidence market, right? The forty- Yep. Few per year are the ones treated. There's the prevalence we believe is about 50. It's very. The difference is very small. Okay. Yeah, just wanted to make sure I got that. Thanks so much. Our next question comes from Dane Leone with Raymond James. Your line is open. Hi. Thanks for taking the questions, and congratulations on the approval of SKYSONA. The question that we've been getting back a lot with the approval of SKYSONA following the approval in TDT is just how you guys are thinking about operating burn as you ramp up these commercial efforts and getting these QTCs online, heading into 2023. Then just any additional color now that you're probably going to get the PRV for SKYSONA as well, on that path to financial stability. Thank you. Thank you. Good morning. I'll take the second part of that question first, and then I'll hand it to Jason for the first part. We have the PRV in hand, right? We do have both PRVs, and as we've mentioned before, we are in the process. We hired a bank to sell the first one. We will sell those sequentially, and we anticipate those about $110 million each. That will provide us a non-dilutive financing going forward. That does put us in a much more stable financial position. I'll pass it to Jason to discuss the outlook for 2023. Yep. Thanks, Andrew. Yeah, the way to think about bluebird bio's cash burn is, you know, we took the significant restructuring activities back in April, and that has really brought our cash burn down. We are driving toward bringing it to about $60 million cash burn by the fourth quarter and hope to perpetuate that into next year. 240, 245 cash burn in 2023. We believe that is sufficient resources to successfully commercialize and launch ZYNTEGLO as well as SKYSONA, and to file the lovo-cel BLA on time in the first quarter of 2023. What the 2023 burn looks like long term will depend a little bit around, you know, how ZYNTEGLO performs and other investments we might wanna make, but we feel well-resourced for the milestones we see ahead for next year. Excellent. Thank you. Congratulations. Thank you. Our next question comes from Mani Foroohar with SVB Securities. Your line is open. Hey, guys. Thanks for the question. I'll add my congratulations on the approval. You talked a little bit about, you know, how your thinking might evolve, about further investments, et cetera, as you see the commercial performance. Could you clarify what are you looking for or what metrics should we be following, to think that, okay, the launch of ZYNTEGLO, lovo-cel, SKYSONA, et cetera, is on track for you guys to return to reinvesting in key areas of growth opportunities? Or is it should we think about cash or breakeven? Are there specific, you know, broad sets of revenue numbers, growth metrics? How should we be thinking, what should we be looking for, as markers of success and a return to investing in the business? Yeah. Mani, I'll take the first part of that question. I'll give the second part to Tom to talk about some metrics. Overall, what you should be looking for is ZYNTEGLO launch performance, and Tom will go into the metrics in a second or types of metrics we'll be looking at. The second thing is filing the BLA for lovo-cel, right? Those are what's in front of us near term. bluebird continues to be focused on very near-term milestones and hitting all of our operational milestones we've done so far this year and we intend to do upcoming in order to put us in a very solid operating base and our future. You should not expect to hear about future investments in the near term, as our focus right now is on our existing three therapies. Tom, maybe you could comment on some of the metrics that we'll be following with ZYNTEGLO launch. Yeah. Hi, good morning, Mani. We're really excited about the launch of ZYNTEGLO, which is well underway. As we mentioned, Wave One QTC network should be online by the end of this month. We're looking at some early indicators of success, which would include things like progress with our QTC network, calls into my bluebird support, patient enrollment form requests, which we've received a good number of patient enrollment form requests already. Patient starts in terms of how many apheresis procedures we can start between now and the end of the year, benefit verification requests. These are just a few. I'm giving you an example of some of the things that we're tracking, and we will, you know, kind of narrow that down and give you an update as we get closer to the end of the year or into next year. Okay. That's helpful, guys. Our next question comes from Luca Issi with RBC Capital Markets. Your line is open. Oh, great. Thanks so much for taking my question. Congrats on the great approval here. Maybe two quick ones. Maybe on the PRV, maybe, kind of what's the latest thinking on extending the runway at this point? And maybe related to the PRV, does your current balance sheet puts you in a weaker negotiating position, or should we assume that you'll be able to get $110 million in redemption fee for PRV? And the second on sickle cell disease, any update there, particularly in the clinical hold below 18 years of age? Thanks so much. Yeah. Thank you. I think I got most of that, Luca. You were breaking up a little bit, but I'm gonna take them all backwards, right? Clinical hold for sickle cell, we're still in correspondence with the FDA. No new update on when that might be resolved, but we're in active discussions. Still on track to file the sickle cell BLA in the first quarter. I think the meat of your question was about the PRVs and the cash runway. We do expect that. You know, we have a number of things that have changed with bluebird bio through the course of the summer, right? We have ATM that is now open. We have two PRVs now in hand. Of course, we're now expecting commercial revenue next year. All those together extend our cash runway. Into 2024. We're in a much better position than we were. We do fully anticipate that we will be able to monetize those PRVs in the range of $100-$110 million each. $110 million is the market rate at this point, and that's what we expect. Got it. Thanks so much. Our next question comes from Yaron Werber with Cowen. Your line is open. Hi, this is Brendan on for Yaron. Thanks very much for taking the question. Congrats on the approval, guys. Just a quick one from us, really. Is there maybe any additional color on any feedback you've gotten from payers so far? Or anything in particular from those negotiations that may or may not impact the initial ramps for the launch that we should maybe be aware of? Just any important next steps we should, you know, kind of be thinking about. Yeah. Yaron, just maybe to clarify, are you talking about ZYNTEGLO or are you talking about SKYSONA? For SKYSONA. Actually, I guess same question for ZYNTEGLO, if there is anything of note. Yep. Tom, would you- Yeah. Let me. Good morning. Let me start with SKYSONA first, just to keep them separated. You know, with SKYSONA we're confident that payers, based on the clinical benefit that SKYSONA provides, obviously is a potentially life-saving, urgently needed therapy in a very devastating disease with no other FDA-approved options. We're committed to working with payers to make sure that payers have access to SKYSONA. Based on its rarity and based on no other options being available, we feel confident that payers will support SKYSONA as well. With ZYNTEGLO, we are several weeks into our launch now, and we are getting a lot of positive feedback from payers. In fact we've had payers publish policies already. We've had multiple contracts signed with both big individual payers but also PBMs. We're getting a lot of good positive feedback and momentum with payers mostly on ZYNTEGLO, and we expect the same on SKYSONA. All right. Great. Thanks, guys. Our next question comes from Gena Wang with Barclays. Your line is open. Thank you for taking my questions, and also congrats on the approval. Two parts. The first one is for the confirmatory long-term data, including, you know, ongoing open label study as well as the commercial patients, what kind of data you would need to be collecting and how often you need to collect them? Regarding the QTC centers, wondering how many patients already identified from these two centers. Also could you remind us if the CALD is part of the newborn screening? Yeah. Let me take the second and third part. I'm gonna pass the first part over to Rich. The QTCs, we're not commenting on individual number of patients within the QTCs. Just to say that we do have patients that are interested. On the newborn screening, we do have newborn screening set up for cerebral adrenoleukodystrophy in the U.S. We believe that currently covers about 75% of the patient population in the U.S. Then Rich, maybe you could comment on the clinical what type of data we're collecting in the long-term study and how we'll follow it up. Yeah. Thanks very much, Andrew. Thanks, Gena, for the question. In terms of the long-term data for the follow-up, first, the 67 patients who've been treated in our clinical studies are all entering our long-term follow-up study, and that's the bulk of that data that's gonna be required for the next 15 years. Any additional data we need, we anticipate is going to come from those patients treated commercially. Can you be a little bit more specific regarding what kind of data? Or, like, you know, would that be insertional mutagenesis analysis or dominant clone? What kind of data you would need to be collecting? Yeah. No. Thanks, Gena, for the follow-up. Yeah, the endpoints are all on ClinicalTrials.gov. Basically it is safety data. It includes insertional site analysis as well as efficacy data, and we're gonna follow them for MFD. Yeah. Just to say that we have the long-term follow-up study. The study is posted on ClinicalTrials.gov, so you can actually see those there as well. Okay, thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open. Hi, this is Wen Jiang for Matthew. I think our questions have been addressed by previous question. Thank you. Thank you. Our next question comes from Raju Prasad with William Blair. Your line is open. Thanks for the question and congrats on the approval. Just curious to know if there's any manufacturing synergies that can be recognized between SKYSONA and ZYNTEGLO. Any color you could give on gross margin kind of at the launch for either would be helpful. Thanks. Raju, thanks for the question. Manufacturing SKYSONA and ZYNTEGLO are actually manufactured in the same plant, both the vector and the drug product. There's a lot of synergy between those two. They are also, treatment takes place at the same QTCs. The way to think about a SKYSONA launch is that it is incremental resources on top of the ZYNTEGLO launch, which makes it a much more cost-effective. In terms of initial margins on a per unit basis, I'd say that the margins are attractive for a gene therapy company, which the margin gene therapy manufacturing is more expensive. There's some fixed costs in terms of the manufacturing plants that will need to be spread over time as we scale. You know, but on an incremental basis, each unit is positive. Our next question comes from Yanan Zhu with Wells Fargo. Your line is open. Hi, thanks for taking my questions and, congrats again. Congrats also, I wanted to add my congrats to the approval. Just, maybe two quick questions. One is, when do you expect to apheresis the first patient, in a CALD launch? The second one is, could you talk a little about the rationale for this being an accelerated approval, based on that, you know, primary endpoint rather than a full approval? Thanks. I'm gonna take the second part first. Following the AdCom and discussions with the FDA, we came to the agreement that the most expedient way to get this to patients was through the accelerated approval pathway with that two-year endpoint on MFD-free survival and to follow up the patients in both our clinical trials and commercially to confirm the durability, not necessarily the product as it was working that, but more so the comparison with the historical controls. That was the discussions we had with the FDA. Tom, can you comment on the first patient? Yes. We are working hard to execute our launch plan based on the PDUFA date and our QTC network will be coming online by the end of this month. We expect to make SKYSONA commercially available by Q4. The first patient will be apheresis in either late Q4 or in the early Q1. I would just layer on that this is a patient population where they're diagnosed and treated fairly quickly. It really is more about when the patients actually come into the system that the treatment happens. Got it. Thanks. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Hey, good morning. Thanks for taking our question. This is Elizabeth on for Salveen. Just a question around the expectations for the first quarter of launch and whether you think there would be a bolus of patients or, you know, whether there are more expectations for a slow and steady launch from your end. Thank you. Go ahead, Tom. Yeah. Hi, good morning, Elizabeth. Let me just clarify. We're talking about ZYNTEGLO versus SKYSONA or are you talking about SKYSONA? SKYSONA specifically. with SKYSONA, because it's such an ultra-rare condition and as Andrew mentioned, patients progress either rapidly or they're not necessarily in the system or in the hospital currently like ZYNTEGLO is. It's, I wouldn't suspect with the small number it's gonna be a giant bolus of patients. Got it. Are there any kind of, you know, magnitude? Is there a magnitude you can kind of help frame that? Or, is there kind of less you can say at this point? Yeah, I wouldn't think of it with SKYSONA in terms of a bolus. It's more random. Based, you know, again, it's a small number of patients and with the disease complexity and progression, it's kinda harder to predict when a patient might come into the system. Understood. Thanks so much. Thanks, Elizabeth. If there are no further questions, I'd like to turn the call back over to CEO, Andrew Obenshain, for any closing remarks. Thank you everyone for joining this morning, and a particular thank you to the entire community that helped get us to this point. It's really a remarkable milestone for the cerebral adrenoleukodystrophy community. Thank you. This concludes the program. You may now disconnect. Everyone, have a great day.