Good morning, everyone, and thank you for joining today's presentation. My name is Courtney O'Leary, Investor Relations at bluebird bio. Before we begin, let me review our safe harbor statement. Today's discussion contains statements that are forward-looking under the Private Securities Litigation Reform Act of 1995, including financial projections in addition to statements of the company's plans, expectations, or intentions regarding development of our clinical programs and commercialization plans following potential regulatory approval. 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. While we may elect to update forward-looking statements in the future, we specifically disclaim any obligation to do so if our expectations change, except as required by law. You should not rely on these forward-looking statements as representing our expectations at any date subsequent to today. Thank you for joining, and I will now turn it over to Andrew. Thanks, Courtney, and thank you everyone for joining us this morning. I'm excited to talk to you today in my new role as the CEO of bluebird and to tell you about the incredible opportunity we have to transform the lives of people with sickle cell disease. bluebird is now a severe genetic disease company. Our journey did not begin with the company split on four November. The work started over nine months ago. In that time, we've built a team of gene therapy experts whom you'll hear from today, and we've significantly reduced our cost structure. We wound down European operations and the associated global footprint. We significantly reduced our real estate, and we eliminated spend on low ROI activities. In the meantime, while all this was going on, we delivered on our operating milestones despite clinical holds and despite splitting the company. We've just submitted our BLA for beti-cel, and our plan for filing lovo-cel is on track for before the end of this year. Now that the split has happened, we're realizing immediate benefits. We have zero distractions. We are laser-focused on launching our three transformative products, and we've allocated our capital and management attention to the most important priorities. The top priority for this team is delivering lovo-cel, our transformative gene therapy to the sickle cell patients and their families. A note before we start. Over the years, you've heard us refer to our sickle cell therapy as LentiGlobin or BB1111. Starting today, you'll hear us refer to it as lovotibeglogene autotemcel or for short, lovo-cel. That brings me to the subject of today, our sickle cell program. You will hear from both our internal gene therapy experts as well as Artisha, a patient with sickle cell disease, and Dr. Smith, a leading treater for sickle cell. Following my remarks, Rich Colvin will discuss the unique profile of lovo-cel for sickle cell disease and review our unique and exceptional clinical data. Rich is not only our Chief Medical Officer, but still regularly sees patients in clinical practice. Virginie Hageman is gonna describe how we significantly re-derisked our regulatory path to BLA. AV is our Chief Regulatory Officer and a luminary in the area of gene therapy. We are then gonna hear the perspective from a treating physician, Dr. Smith, the Director of the Adult Sickle Cell Program at VCU Health. Dr. Smith is one of the most published authors in sickle cell disease. Finally, Tom Klima, our Chief Commercial Officer, is gonna discuss lovo-cel and the commercial opportunity and our priorities. Tom has previously launched three cell therapies. At the end of the presentation, we'll be joined by other team members for Q&A, including CFO Gina Cunkelman and Kasra Kasraian, who oversees technical development operations and is a bluebird bio and gene therapy veteran. Underpinning our sickle cell program is the critical mass and leadership of bluebird bio in gene therapy. Here is a look at bluebird bio, by the numbers, and they are impressive. We have the largest and deepest ex vivo gene therapy dataset in the world. We have 485 years of patient experience with bluebird bio gene therapies, and that data's been generated from the treatment of 170 patients in eight clinical trials. With our rich history in gene therapy, we have up to 10 years of follow-up across all of our lentiviral vector programs. This dataset is the foundation for the potential launch of three first-in-class therapies for sickle cell disease, for beta thalassemia, and for cerebral adrenoleukodystrophy. With these, we have the opportunity to benefit up to 22,000 patients in the US. Now, behind all this incredible work is a team of more than 500 Bluebirds. We have the best, most experienced team in gene therapy, led by tenured Bluebird leaders and recent additions. This team has set Bluebird up for success. We are poised to unlock significant value for both our patients and for our shareholders. Sickle cell is a debilitating disease. Rather than try to capture the impact with a data slide, I wanna share the experience of one patient, Artisha, whose personal experience brings to the fore the difficulties encountered by people living with sickle cell disease. Here's Artisha in her own words. With sickle cell, it really is day by day of how you're gonna feel. It's hard to plan different things because we don't know how we're gonna feel from day to day. It's hard, you know, to really have a normal life like other people. One day I may not feel like getting out of bed, or maybe it take two hours for my legs to stop hurting. Even things like a shower. Like, sometimes the shower makes me out of breath, and so after I get out the shower, I have to sit down for 30 minutes. It's really hard living with sickle cell. It feels like glass running through your veins. Or maybe how I describe it sometimes is someone hitting me with a hammer. My doctor has seen me through the roughest times ever. Anxiety, depression, being scared of if I'm gonna be able to take care of my son. My mother, unfortunately, was not educated on sickle cell when I was born, and I had to learn for myself. Even when I was 25, and I had my stroke, I had no clue that a stroke was a possibility. Like, I knew that I would have crisis all my life. As a child, I had pneumonia quite a few times, but a stroke, that blindsided me. If you don't have sickle cell, you absolutely do not know what it's like. I can talk to you until I'm blue in the face, and there's nothing I can tell you to make you understand. The pain alone is indescribable. Not only when you're in a crisis, we lay in a bed in pain all the time, and most of us don't wanna go to the emergency room when we're in a crisis. We will suffer, and that's suffering in silence. That is just lonely. Lonely is not even the word to describe it. When you're in the hospital, you're terrified. People die of sickle cell. When you're in the hospital, you really don't know if you're gonna make it out. Having sickle cell is trying in every way. It affects every aspect of your life. If you have sickle cell, you don't have a normal life. Artisha captures in her words better than any data slide ever could the experience of sickle cell disease. The intolerable pain, "Glass in my veins," is what is usually associated with sickle cell, but it is so much more. One in four patients have a stroke by the age of 45, and today, organ failure is the leading cause of death among patients with sickle cell disease. A full half of people with sickle cell die before the age of 50. Sickle cell disease has historically been ignored and severely underappreciated. As a disease that primarily affects the Black community, there's been a significant underinvestment in innovation for patients, and change is long, long overdue for the one in 365 Black children born with sickle cell disease in the U.S. every year. lovo-cel has the potential to change the story. lovo-cel provides a potentially curative one-time therapy that has demonstrated the ability to eliminate pain crises and has the potential to transform the lives of people with sickle cell. bluebird is focused on delivering lovo-cel for patients and their families, and we expect to be the first in the US for the treatment of hemoglobinopathies. First with a gene therapy approved and available for hemoglobinopathies in the US, starting with beta thalassemia in 2022. We believe it is also likely that we will have the first gene therapy approved and available in sickle cell disease with lovo-cel. As you will hear today, this belief is based on the strength and duration of our clinical data, the significant progress we have made finalizing our commercial manufacturing and analytical plans, and our extensive productive engagement and alignment with the FDA on the high standards they are setting for the approval of gene therapies for a disease as complex as sickle cell. Today, we're gonna talk about our path to approval for lovo-cel and how we are preparing for the commercial launch. Now I'm gonna turn it over to Rich to discuss the exceptional data generated in our clinical trials. Thanks, Andrew, and good morning, everyone. Lovo-cel truly has an exceptional clinical profile. As a physician scientist who has had the privilege of working on therapies for hepatitis C and HIV, two diseases in which science and medicine have had enormous success for patients, I believe that lovo-cel has the potential to be just as transformative for patients with sickle cell disease. Lovo-cel is the most mature gene therapy being studied for the treatment of sickle cell disease. In our clinical studies, we have treated 49 patients with up to six years of follow-up and have over 100 patient years of experience. There have been no severe vaso-occlusive events, which are the major problem patients with sickle cell disease face among the first 19 patients in group C of our study, HGB-206. We'll come back to this in a moment. Along with incredible efficacy, we understand the safety profile of lovo-cel, which is generally consistent with the risks of autologous stem cell transplant in patients with sickle cell disease. Our technology is transformative and backed by clinical data that we have accumulated over the past six years. As we move across this slide from left to right, we follow lovo-cel from the molecular level through our clinical studies and finally to how we monitor it in patients for the long term. Across our core three programs, meaning sickle cell disease, beta thalassemia, and adrenoleukodystrophy, we custom designed each gene therapy at the molecular level using a specific lentiviral vector and an individualized manufacturing process. On the left, for sickle cell disease, the unique design our bluebird scientists built into lovo-cel drives expression of hemoglobin A-T87Q, which is designed to function as an anti-sickling variant of naturally occurring adult hemoglobin that prevents the sickling of red blood cells and reduces levels of abnormal sickling hemoglobin, also known as hemoglobin S, that causes the symptoms of sickle cell disease. Further, our technology is deeply studied in patients. Over 300 patients have received lentiviral vector gene therapies for severe genetic diseases over the past 15 years. These diseases include sickle cell disease, beta thalassemia, and cerebral adrenoleukodystrophy. Research to date has shown robust, durable efficacy and has enabled us to better understand the safety risks. We have more than 100 patient years of experience with lovo-cel. Importantly, our technology is traceable, and this is due to our ability to detect the precise insertion site of the lentiviral vector in the genome. This was key during our swift analysis of the safety event this year and for monitoring patients going forward. For the patient with sickle cell disease who was diagnosed with leukemia, we were able to quickly show that vector insertion was not responsible for any change in gene regulation or gene expression nearby the insertion site. We therefore concluded that the insertion did not play a role in the development of leukemia. Other gene therapy modalities, like gene editing, cannot be tracked this precisely or this easily. In fact, this past year we advanced the entire field of gene therapy through key learnings following the safety event that occurred in our sickle cell disease program. As a reminder, the clinical holds on our trials for lovo-cel were lifted back in June of this past year. As a result of our team's swift analysis and robust data set, we highlighted the risk of leukemia that patients with sickle cell disease have at baseline and identified ways to mitigate that risk during lovo-cel treatment. We put in place systems for better pre-screening, improved the treatment process resulting in better outcomes, and we increased the monitoring post-treatment of our patients in our studies. Further, we energized the field to commit to additional study of these areas and believe that these key learnings will allow us to better serve patients and the broader community going forward. Let's now focus on the key data regarding the severe vaso-occlusive events and the truly transformative nature of lovo-cel. Many of you have seen this efficacy slide from patients in group C of our HGB-206 study that was presented by Dr. Alexis Thompson last year at ASH. This study shows the severe vaso-occlusive events from the first 19 patients in group C from the two years prior to receiving lovo-cel and then for up to two years after receiving lovo-cel. What is a severe vaso-occlusive event? It is a pain crisis that requires a patient with sickle cell disease to be admitted to a hospital and receive intravenous medications. It is also a life-threatening event. Any severe vaso-occlusive event can result in fatality. Each lane in this graph represents the severe vaso-occlusive event the patient has over time. The X-axis is time, and the blue lines represent the two years prior to therapy with lovo-cel. The red diamonds represent severe vaso-occlusive events. There are a total of 165 severe vaso-occlusive events in just 19 patients before treatment. As you can see on the right, no severe vaso-occlusive events for up to 24 months following treatment. Not a single severe vaso-occlusive event. We couldn't be more thrilled to see these results, especially for patients with sickle cell disease. To put these numbers in a human context, each severe vaso-occlusive event represents a significant traumatic and painful experience, a hospitalization causing disruption in life, impeding the ability to go to school or to work, and always with the possibility of becoming fatal. In our opening video, you heard Artishia describe a vaso-occlusive event as being hit by a hammer. One of these patients, second from the bottom, had 21 severe vaso-occlusive events over the previous 24 months. For this patient and the other 18 patients, these events have been eliminated. Eliminated after treatment, thereby underscoring the potential curative nature of lovo-cel. Imagine how this has transformed these people's lives. As our safety database continues to grow with some patients having been treated more than 6 years ago, we are learning that the risk for patients with sickle cell disease is typically related to the stem cell transplant procedure rather than the lovo-cel itself. At an exit interview 2 years after being treated in the study, one patient said this when asked what advice he would give other patients considering lovo-cel. Advice I would give them is that for me, when I talk about it with other patients, I always say that it's the best decision in life that I have ever made. The best decision." We're looking forward to ASH 2021 in December, as we are super excited about the data we're presenting. As you've likely seen from the abstracts, Dr. Tisdale will show data from more patients treated in study HGB-206, and another year of clinical benefit during long-term follow-up for treated patients, which continues to support our goal of providing potentially lifelong patients, lifelong benefit for patients with sickle cell disease. The paper also dives deeper into our molecular understanding of why patients in group C have had such successful clinical outcomes. Dr. Walters is presenting data demonstrating sustained improvements in patient-reported quality of life for up to 24 months post-treatment. These data show the patient's view on how lovo-cel transforms their lives. It is remarkable that at ASH we are not only showing data that demonstrate how our gene therapy works at the molecular level, but we're also showing data on how it is making a meaningful difference in the daily lives of people with sickle cell disease. These updates will continue to grow the knowledge base of lovo-cel for sickle cell disease, thereby bolstering confidence among regulators, healthcare providers, and the sickle cell disease community as we prepare to bring lovo-cel to patients. Now I want to turn it over to AV to talk about the final steps in the regulatory pathway to do just that. Thank you, Rich, and good morning, everyone. I'm thrilled to be here today to share with you the progress we've made to de-risk our path to BLA for lovo-cel for the treatment of patients with sickle cell disease. Over the past few years, we've successfully established the critical building blocks for this BLA. As a leader in gene therapy, we've gained some learnings from being first, and we are now poised for success as we have generally aligned with FDA on the content of our BLA and on the steps left for submission. On the clinical regulatory side, we should all remember three things. First, we have reached general agreement with the FDA on the clinical data required to support our BLA review. Second, our BLA data package at the time of submission will be robust. It will include data on approximately 50 patients with follow-up up to seven years. In our pivotal cohort in study HGB-206, referred to as group C, we will have approximately 30 patients available for the primary endpoint with a minimum of 18 months of follow-up. I would like to emphasize that HGB-206 is the largest gene therapy study conducted in patients with sickle cell disease to date, and it has a clinically meaningful primary endpoint. The third thing to remember is that we actually have treated all the patients in HGB-206 group C who will form the primary basis of effectiveness for approval. From a regulatory standpoint, we've de-risked our clinical path to BLA as much as we can at this time. Now with a solid foundation for our BLA established on the clinical side, we can pivot to what is on critical path moving forward. It will be no surprise to you that it is all about manufacturing. Manufacturing is typically on critical path for gene therapy products because these products are complex to manufacture and because the FDA has set a high bar for their quality. For lovo-cel, we're in the final stretch of the CMC execution, and the last building blocks to BLA submission are related to the improvements that we've made in the past couple of years in the manufacturing of both our BB305 lentiviral vector and our lovo-cel drug product. These improvements were conducted to ensure we would meet patient demand at launch with a robust and scalable process. Hence, it was critical for us to clarify and confirm our detailed CMC path to BLA with the agency to ensure we would generate the CMC data required for submission. I'm pleased to share with you that we've done just that. Last year with the FDA on the reg CMC roadmap to BLA submission, we aligned on the key requirements. We agreed that we could use CMC data only to demonstrate comparability for the changes we've made. The FDA did not request any clinical data to demonstrate comparability. This was a major de-risking event for our program. More recently, we went even further in our discussions with the agency and reached alignment on additional details of our CMC path to BLA and aligned on the fastest scientifically justified steps to demonstrate comparability. It is also important to note that in the second half of this year, we reinitiated our HGB-210 phase III study. We plan to start the treatment of patients in this study in early 2022 with drug product manufactured in our commercial facility and with the totality of the process changes to support commercialization implemented. Overall, de-risking the CMC path to BLA was key for us, not only because CMC is on critical path, but also because if you picture a BLA, the CMC piece, the CMC modules are generally the largest part of these BLAs. The agency has even acknowledged that they spend about 80% of their time on their review of these CMC modules and only approximately 20% on clinical. Based on these key achievements, we expect to submit our BLA for lovo-cel in Q1 2023. We've come a long way on the path to submission, and we are now executing on the final stretch of the CMC package. This final stretch is depicted on the next slide. First, to provide context on this final stretch, let's take a deeper dive on the manufacturing improvements that we've made and why. We switched from adherent lentiviral vector, which is manufactured on trays, to suspension lentiviral vector, which is manufactured in a bioreactor. This change has resulted in a tenfold increase in output and has lowered costs. We also decided to launch lovo-cel from commercial facilities for both our vector and our drug product. This will allow us to meet long-term supply demand and to meet commercial compliance requirements. Lastly, we've optimized our drug product manufacturing process based on extensive experience gained during clinical trials in patients with sickle cell disease, as well as our experience in going through marketing authorizations in other programs. This will allow us to have a robust and scalable manufacturing process at launch and should limit the number of post-approval changes. Overall, these improvements will support the commercialization of lovo-cel and ensure we meet patient demands. Switching to execution, there are four major CMC blocks of work leading to BLA submission in Q1 2023. We will have already completed two of them. Leveraging our RMAT designation, we will be moving forward in lockstep with FDA through these CMC evidence generation milestones. What are these key steps? Step one, which is depicted with the first green bubble on the bottom left, is all about analytical assays. Across the industry, there have been a number of delays related to analytical assays. These delays have impacted both large and small drug developers alike as the FDA is appropriately setting a bar that is high for the release and characterization of advanced therapies. At bluebird bio, I'm pleased to share that we have aligned with the agency on all the assays that we need for the lovo-cel BLA, including functional potency assays, which usually take a long time to develop. At this time, I'd like to emphasize that all our analytical assays, including functional potency assays, have been developed. Check. Steps 2 and 3 are all about commercial process validation, which means demonstrating consistent manufacture of a commercial process in the facility intended for launch. For our vector, we have completed the manufacturing of these validation lots. Check. We are now on the cusp of starting the manufacture of our drug product validation lots. Finally, the last step is about analytical comparability. This is where we collect and analyze all the manufacturing data generated from our commercial processes in our commercial facilities and compare them to the manufacturing data we've generated in clinical trials in clinical facilities. Here's the key takeaway from this slide: We're on a solid trajectory towards lovo-cel BLA submission in Q1 2023. Our team is executing on the plan that we've agreed upon with the FDA. Now, I have the privilege to introduce Dr. Wally Smith, who will share his perspective as a leading physician with more than thirty years of experience in treating patients with sickle cell disease. Dr. Smith is a professor at Virginia Commonwealth University in the Department of Internal Medicine and serves as the director of the Adult Sickle Cell Program at the university. He also serves on the board of the Foundation for Sickle Cell Disease Research and is a member of the Medical and Research Advisory Committee for the Sickle Cell Disease Association of America. Dr. Smith has extensive publications in the field of sickle cell disease as far back as 1989, with a clear focus on patient experience. He's a constant voice and face in the world of sickle cell disease. Welcome, Dr. Smith. Thank you and good morning. I'm excited to be talking to you today. It is an exciting time in the sickle cell disease community after decades of stagnation. In therapies for patients with sickle cell disease, we are seeing significant advances being made in these therapies with significant investment for the first time in changing the face of sickle cell disease. This is an opportunistic moment that we don't all want to miss. The patients don't want to miss it. The physician community sees the promise. The atmosphere is pregnant with the potential for improvements in future therapies and to make a meaningful difference in the lives of some patients who've seemed forgotten in the past. I just wanna let you know that Bluebird has been with us from the start, listening to patients, building trust and commitment. This is an untrusting community, and it's taken a while to win their trust over. bluebird bio has been working very hard to listen to the community, to hear their stories of woe and neglect, and to turn those into stories of feeling supported, and feeling like somebody cares for a change. The patients could not be more deserving. I've been doing this for 30 years, and I've watched HIV pass us by, and advances there, cystic fibrosis pass us by, and advances there, hemophilia pass us by, and advances there, and of course, cancer. We've seen these deserving diseases get the attention that they deserve, but we have not seen that in the area of sickle cell disease. The need is great. This is a devastating disease. It impacts every aspect of their life. I often say to know sickle cell disease is to know medicine. Let me just give you an example of a young lady that's been involved in the education program that bluebird bio has launched. She's my patient, and she was excited about what she heard going on, and now she's just had a stroke. I don't want her to have another stroke before we do something to interrupt this disease in her lifetime. We need the advances and the improvements of the therapies that she's already on, but we need advances and improvements in therapies that are potentially curative. We hope that you understand that those advances take time and money and investment. You've seen some of bluebird bio's data. You've seen some of the difficulties recently encountered with determining whether this therapy or whether the myeloablative regimen or whether sickle cell disease itself is somehow leukemogenic. We're still investigating that, but in the meantime, we think we've cleared that it's not the therapy and that there is room to continue with the trials that are ongoing and to put this important option in the hands of providers as soon as possible. The providers are ready. We are ready in the front lines of the sickle cell community, the treating community, but also the troops that are in the primary care arena and in the emergency care arena are also ready to join with us. Organizations like the American Society of Hematology is training and making visible this disease and training, doctors who have any interest at all in starting sickle cell centers, just like you see cancer centers, to support, to educate, and to treat these patients the way that they need. I'm asking you to join us. We're climbing Mount Everest. It's a long way up. We're somewhere around milepost one, but we need you to join us and help us make the climb. Thank you very much. Dr. Smith, thank you for your perspective from what you've seen over your decades of experience. We agree these patients are deserving, and now is the time to bring forward new therapy options for patients with sickle cell disease. Good morning, everyone. My name is Tom Klima, and I'm the Chief Commercial Officer at bluebird bio. bluebird bio has been committed to meaningful change for people with sickle cell disease and their families for more than a decade, and we're extremely excited about the opportunity to deliver on the promise of gene therapy. Our launch preparation is well underway and is defined by deep expertise rooted in years of patient and market insights. Today, let's examine three critical components of our launch preparation, enabling us to bring lovo-cel to patients in need following potential approval. First, let's talk about a snapshot of our partnerships and educational efforts, which will be the foundation for gene therapy adoption. I'll summarize our confidence in value recognition that we expect will lead to coverage and reimbursement for lovo-cel. Finally, a look at our plan to enable a targeted and experienced treatment network that maximizes proximity to patients and becomes a unique advantage for bluebird. Sickle cell represents a blockbuster opportunity, and bluebird is uniquely well-poised to bring a potentially curative one-time therapy to this historically underserved patient population. As previously stated, there are over 100,000 people with sickle cell disease in the United States and over 20,000 who are initially addressable based on the patients in our clinical trials. Now, for the first time, take a look at some of the insights we have gained and why we believe lovo-cel has the potential to be a blockbuster therapy. Spanning the last six years, we've been conducting market research across every influential stakeholder group. We have learned a tremendous amount, especially from the collective patient community. Let me just share a few highlights today. All patients recognize the impact of their disease, with 6 out of every 10 patients classifying the impact as severe, which means they spend a lot of time trying to manage their disease. They really highlight not only the physical impact of sickle cell disease, but also the impact of their social and emotional well-being. Turn now to the middle circle and look at how most patients also report being extremely dissatisfied with current treatment options, saying that treatment options today are insufficient for managing their disease. Finally, at the bottom, all patients polled are concerned about their future, and I can hardly imagine being in a situation where you can't even plan for the road ahead or plan to adopt some of the impact of sickle cell disease. One thing is clear, patients, as Dr. Smith said earlier, are ready for better options. Let's dig a little deeper, and as we just reviewed, there is pervasive dissatisfaction with current treatment options. Now let's look at the tremendous excitement that we're actually seeing for lovo-cel from both patients and physicians. Starting with the top two circles are the most common need and the greatest need from both patients and physicians. They share the common view that new treatment should address their disease and eliminate VOEs, which also reduces hospitalizations and other complications. Remember, Rich earlier discussed the group C cohort of HGB-206, where lovo-cel completely eliminated severe VOEs. Now turn your attention to the red middle circle that on the left-hand side, and another compelling, probably the most compelling point to me, where nine out of ten patients that we surveyed showed a strong interest in lovo-cel after viewing the target product profile. After seeing the profile, they said they would act by initiating a treatment conversation with their physician. Now, as we turn to HCPs, please look at the bottom circle, where seven out of ten target physicians report a high likelihood of adopting lovo-cel within the first six months of launch. Again, that's after seeing the target product profile. The need in this large and underserved patient population is clear. For both patients and physicians, they are excited about the potential that lovo-cel can offer. bluebird continues to be committed to meaningful change in sickle cell disease because we know that education, support, and advocacy are essential for patients when gene therapies are approved and available. There are more than one hundred national, regional, and local sickle cell organizations, and we have been working across this network to provide support and partnership to help advance gaps in the healthcare system in the treatment of sickle cell disease. We've also convened leadership forums with leading minority health organizations to educate on relevant policy needs, which include both health disparities and access challenges. No one else in industry understands the need and the network of sickle cell disease organizations better than we do, and we remain committed to our partnerships, educational efforts, and support, which ultimately is gonna help more patients gain access to new and curative therapies. We are also confident that lovo-cel will deliver value as a one-time, potentially curative treatment for a devastating disease with significant cost to the system. Now, these numbers are not on this slide, but when looking at patients with a history of VOEs and considering medical encounters, cost of care ranges between $2.5 to 5 million per patient. We're also seeing an overall increase in cost of care with the introduction of supportive chronic therapies in recent years. We've been working with U.S. commercial and government payers now for over three years, and we believe they have not only an appreciation for the unmet medical need in sickle cell, but also for the value lovo-cel brings to patients and to the system. There's no one-size-fits-all approach to access and reimbursement for gene therapy, and we understand the unique needs and priorities of patients, providers, and payers. Our focus is on value recognition and ensuring speed and quality of access, which will be achieved with an integrated payer-provider approach that is designed to be flexible and to meet the needs of stakeholders with the common goal of providing access for patients. We spent many years gathering insights and developing our access strategy, and we are now moving quickly into execution mode in the U.S. One thing I'm most proud of when I look at the bluebird team is the collective years of experience in sickle cell disease, hemoglobinopathies, and within the transplant community. It's simply amazing and cannot be matched. Having said that, let's turn now to our qualified treatment center or QTC plan. We expect to launch beti-cel for beta-thalassemia next year, which will set the groundwork for groundwork for success in sickle cell disease, providing a head start in awareness, access, and a framework for operational excellence. 100% of the beta-thalassemia QTC sites are also target sites for sickle cell disease. As we click through this map, you'll see a concentrated patient population with high degrees of overlap between top beta thal states and sickle cell states. We expect to leverage these synergies, and ultimately, we plan to establish lovo-cel QTCs within a reasonable proximity to patients, providing seamless access to therapy. We understand the multifaceted aspects of launching gene therapy, and we are in high gear focused on executing our strategies that will deliver for patients in need. We're going to be first with beta thalassemia in the U.S., which gives us a head start and uniquely allows us to lay the foundation for success in sickle cell. As I mentioned, our launch plans are in high gear, and we are focused on execution to realize the blockbuster opportunity ahead of us. I'm gonna turn it back to Andrew for some closing comments. Thanks, Tom. Here are the key takeaways from today's presentation. We have an impressive ex vivo clinical data set, the deepest and largest in the entire industry. We have a robust file that meets all of the FDA agreed upon deliverables and a clear path to regulatory filing in Q1 2023. We expect to be the first with a gene therapy approved and available for hemoglobinopathies in the US, certainly for beta thalassemia and very likely for sickle cell disease. We have a blockbuster opportunity and are laying the commercial groundwork now. This sets up lovo-cel to be the most important treatment option for patients with this devastating disease. The team is focused. We've set ourselves up for success and are ready to execute and unlock significant value for our patients and for our shareholders. Last, let me close by thanking the sickle cell community and patients like Artishia. They have not only participated in our clinical trials, but have educated us on their often poor experience with the healthcare system and educated us on the true severity of the disease. Without our decade-long collaboration, none of this innovation would be possible. I'm excited to continue this partnership and together bring a new reality to a community that has been ignored and underserved. With that, I'd like to open it up for Q&A, and we ask folks to limit their questions to one per person so everyone online can participate. Thank you. Operator? Thank you. To ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Yaron Werber with TD Cowen. Your line is open. Great. Thanks for taking my question. Really appreciate it, and thanks for doing the presentation. Maybe my question really has to do with, give us a little bit of a sense, is the analytics that you're doing gonna be similar to the analytics so comparability for beta thal? And what did you end up doing for the potency assay? It sounds like it's analytics only. Did you need to actually show some kind of a direct effect, or did you just need to show some kind of release specs? Thank you so much. Thank you, Yaron, for the question. This is Andrew. I'm gonna pass that question over to Kasra. Go ahead. Thank you. Thank you and good morning. What the FDA required was that we develop a functional potency assay that has a direct effect and shows a biological effect. It wasn't just about a release assay, but they wanted a direct biological effect. I think A.V. at least alluded to that we got agreement with them on our functional potency assay, both for the vector and the drug product. Kasra, we've done that both for thalassemia and for sickle cell. Correct. Yeah. Thank you. Next question. Our next question comes from Cory Kasimov with JP Morgan. Your line is open. Hey, good morning, guys. Thanks for taking the question. Wanted to ask you about future pricing strategy here. I realize this is pretty far off for sickle cell, but not so much for beta thal. You know, a lot of thought and discussion went into this before you launched in Europe, and given how that launch went and the differences in payer systems, how should we be thinking about the U.S. on this front? It's pretty informative for our model on how to think about these products. Thank you. Thanks, Cory. Just I'm gonna make a comment first and pass it to Tom. Just that the U.S. and Europe are fundamentally different markets. In our view, one does not bear on the other, but I can pass to Tom to elucidate more. Yeah. Thank you, Andrew, and good morning, Cory. It's a good question. We've been thinking about price now for quite a while, and as Dr. Smith said, sickle cell is a devastating disease which impacts both the physical and emotional well-being of patients. As a reminder, the cost to the system is high. Patients with a history of VOEs cost between $2.5 to 5 million per patient over the course of a lifetime. We've been really focused on delivering value for patients, and lovo-cel will be priced according to the value that it brings as a potentially curative one-time therapy. Next question. Our next question comes from Mani Foroohar with Leerink Partners. Your line is open. Hey, thanks for taking our question. I guess more of a forward-looking question around how to think about margin profile and as you approach a commercialization in the US and elsewhere. How should we think about the relative absolute expense per dose of a patient commercializing at the scale you expect for beta thal? H ow should we think about the extent of operating leverage as you layer on sickle over time? Is that something that we'd expect the implied cost for a patient to come down over time, or is that a relatively fixed cost given the sophistication and complexity of the manufacturing? Thanks for the question. I think this is a question really I think about scale and COGS. What we've been doing over the course of the last couple of years is to make sure that we have a scalable and robust manufacturing process. That process is gonna, you know, over time, obviously, as we get volume, that of course like anything in the biotech industry, costs come down over time with volume. We're very confident that we'll have a financially strong business going forward. I'm not gonna comment on exact numbers or COGS. That's not something. It's way too early to comment on, and it's not something we'll comment on in general. We are, you know, especially with the U.S. market, very pleased with I think what the impact that we can make on patients, the value that we can create for the market. Then we of course internally are thinking very hard about how to make sure we can make a robust and scalable commercial manufacturing program that fits with that. Thank you. Just to add to that, this is Tom. As you think about the commercial footprint, as I mentioned earlier, there are a lot of synergies. Keep in mind that the QTCs are the same. As we think about scaling our footprint in the field, we can leverage the synergies with our beta thal launch as we get to sickle cell. Great. Thank you. Great. As a quick follow-up, I... You talked a little bit about the scale and the synergies and costs coming down over time, which we've seen across a lot of biotechnology products. Obviously, we're in a special place right now in terms of the supply chain, for sophisticated manufactured products like the components to your therapy. That's gonna change over time. Do you see the cost of components or further elements of the manufacturing infrastructure that could become cheaper or be outsourced over time as we see more cell therapies and gene therapies and transplant medicines like yours come to market? I'm thinking of the continued mainstreaming of CAR-Ts, for example. Does that have a cost input impact for you guys? I think I understand where your question's going. In general, we're not gonna get into the different components of COGS or how that's going to change. Yes, as we gain experience, as we gain scale, naturally we have learnings, and naturally we have economies of scale that will come across all elements of our supply chain. I think Tom mentioned the QTCs, right? We will very likely treat both thalassemia and sickle cell patients in some of those same QTCs, so there's an efficiency there. That's a supply chain question, I guess. In terms of actually the manufacturing, of course, right? We're learning all the time. It is a new area, as you point out, and we're applying those learnings to make ourselves more efficient, to make better products, and to reduce costs. Great. Thanks, guys. Maybe just Kasra, go ahead. Yeah, just to add on to what Andrew already said, we've already implemented the suspension vector process, which has had a tremendous impact on reducing costs because we've increased output by 10-fold, which reduced manufacturing costs and testing costs. Yeah. Great. On to the next question. Our next question comes from Luca Issi with RBC. Your line is open. Perfect. Thank you for taking my question. This is Lisa on for Luca. Just one on operations, post the split with 2seventy bio bio. Can you give us a sense of how the transition has been progressing since the split from an operational standpoint? For instance, what percentage of the workforce has stayed with bluebird bio versus moved over to 2seventy bio bio? And maybe how do you see the headcount here going forward? Thanks. Sure, Lisa, thanks for the question. I'll take the first part of that, and I'll pass the question about our employees and birds over to Gina. We've been very stable throughout the year. We actually have been doing this work now for almost nine or 10 months. four November was not the start of this journey. In fact, most of our birds knew which side they would go to as early as March, and we've been operating internally as different companies. The November fourth split date, in fact, was a momentous time for us to, I think from a public-facing side, but from internally, it was a usual workday, right? We were at the office and continuing what we've been doing for nine months. I'd say the split has been very smooth in that regard. We have all felt, after November fourth, a real increase in our ability to focus and to have the split behind us and to be able to execute on what we're trying to execute day to day with no distractions. On the bluebird's question, I'll pass it over to Gina. Sure. Thanks, Andrew, and good morning, Lisa. This is Gina. Maybe just a quick answer on the number of birds that we have. Right now, we have just over 500 birds. We've done some right sizing of the organization earlier during the year, and all significant changes to our headcount have already been implemented, and we expect our headcount to remain approximately flat through 2022. Thank you. All right, on to the next question. Our next question comes from Jason Gerberry with Bank of America. Your line is open. Hey, guys. Thank you for taking my question. Ahead of ASH, can you just confirm, so will we see all 30 patients from Group C with the 18-month minimum follow-up? Part of the reason I ask is, as we think about the impact that immune suppression could have, you know, pre-infusion on eliminating VOE events, just sort of curious how the profile's gonna look beyond, say, 12 months. Curious to get any perspective you may have in terms of how that immune suppression may lower VOE event rate in that sort of first year. Thanks. Hi, Jason. I'm gonna pass that question over to Rich. Yeah. Thanks, Andrew, and thanks, Jason, for that question. We're very excited about ASH this year. For the sickle cell program, we're going to have three presentations there. The one I think you'll be interested in based on your question is the one from Dr. Tisdale. In his presentation, he's going to not only show those 19 patients that we showed last year at ASH and another year of follow-up for those patients, but there will be additional patients that have been shown. We're excited because you're gonna see mostly similar data to what you've seen so far in those 19 patients, where there were no VOE following treatment and the patients did quite well. Thank you, Rich. On to the next question. The next question comes from Dane Leone with Raymond James. Your line is open. Hi, thank you for taking the questions, and congratulations on the updates. Just wanted to ask the timeline question on the regulatory front for sickle cell. With the study restarting with HGB-210 in the early part of 2022, and the follow-up required of 18 months of 30 patients. I'm still trying to understand what the contribution factor needs to be from HGB-210 for the regulatory submission in sickle cell. Just trying to sort out, your team said several times on the call that you expect to be first approved out of any of the gene therapies for sickle cell in the U.S. I think Vertex has stated on their most recent earnings call that they'll have a filing, submission, by the end of 2022. Is there something to that you could maybe reconcile for us? Thank you. Hi, Dane. Thanks for the questions. I'm gonna take the second part of your question first, and then I'm gonna pass it to AV for the first part of your question. So we're not gonna comment on the specifics of the clinical and CMC path forward for CTX001. That's a question for Vertex and CRISPR. What we will comment on is our own path, and we believe it is very likely that we will have the first approved and available ex vivo gene therapy for sickle in the US. We're very confident we'll have the first approved and available gene therapy for hemoglobinopathies with the beti-cel launch in 2022. Now, our belief there is based on decades-long experience in gene therapy, and as you've heard today, we have more clinical experience and more FDA experience with ex vivo gene therapies than anyone in the field. We've aligned with the FDA on the clinical and the CMC requirements that we've either met or will meet in the near term. We have a very clear path forward, and we're executing against that. Now, regarding the HGB-210 question, I'm gonna pass that over to AV. Thanks, Andrew. I think there are two parts to the answer to your question. I think first it's important to remember that we have treated all the patients in HGB-206 that will form the primary basis of approval from a clinical standpoint for the BLA. That means we don't need HGB-210 from a clinical perspective. Two ten is important because, as we explained earlier, we are restarting treatment of patient in early 2022, and the drug product that will be used in that study is manufactured in our commercial facility, and we need to generate that data to demonstrate analytical comparability. It's the CMC data that we need from HGB-210 that is important for the BLA. As we stated earlier, we believe we will have all the data that we need for the BLA from HGB-210 on the manufacturing side by mid-2022. Thank you, AV. Okay, Thank you. On to the next question. Our next question comes from Raju Prasad in William Blair. Your line is open. Thanks for taking the question. Just wanted a little bit of color on the HGB-210 CMC requirements. You mentioned kind of the scientifically justified comment. I was just hoping maybe a little additional color on the types of like assays and requirements there. Just wanted to get, you know, just broadly on a commercial perspective, you know, there's gonna be kind of several sickle cell gene therapies over the next, you know, say, four to six years potentially coming out. Just how are you thinking about differentiating commercially once, you know, multiple competitors have hit the market? Thank you. Yeah. For that one I'm gonna pass the first part of your question over to AV, and then the second part of the question over to Tom. Go ahead, AV. Thanks, Andrew. I think in terms of the 2seventy CMC requirements, and I'll pass it to Kasra afterwards so he can provide additional color, but from a regulatory CMC point of view, I think it's important to remember that we've aligned on the plan with the FDA with regards to reg CMC. We've and what that means is we've aligned on the statistical methods that we need to use for demonstrating comparabilities. We've agreed on the assays themselves and on the criteria that we need to use for comparability. As I mentioned earlier, we've had actually quite detailed discussion with the agency, and I'll turn it over to Kasra to provide additional color from a CMC perspective. I think you covered most of the items, AV. Just to go a little bit deeper, I think with the FDA, with regard to analytical comparability, we've agreed not only on the typical release assays that we need for comparability, but we also are adding additional characterization assays to further support our comparability, and we're completely aligned with the FDA. We're doing more than just the release assays to verify comparability. Thank you, Kasra. Tom, you wanna take the second part of that question? Yeah, absolutely. Good morning. This is Tom again. Keep in mind that there are over 100,000 patients in the United States with sickle cell disease and over 20,000 patients that we believe are initially addressable based on the patients studied in our clinical trials. Just to remind you, as Dr. Smith said, the need is great. The market research and the physicians we've worked with and the patients we've talked to express a high level of dissatisfaction with therapies available today. I'd like to highlight that with more new therapies, the number of new therapies coming for patients really is good for patients, and we believe that multiple therapies can exist. Having said that, Bluebird has the unique opportunity to launch first in beta thalassemia. We have a deep understanding of our QTC network and have been working with our partners in the clinic for over three years now, just even longer than that when you look at the clinical trials. Going forward, we will leverage those synergies from our initial launch into sickle cell disease. Then just the last thing to summarize, we talked about this earlier, but we've been longstanding partners in the sickle cell community for a long time now, and we remain committed to that sickle cell community. Thank you, Tom. Just to add on, I think the question also referenced some of the news flow about some first-in-human studies that are starting from a number of players, and we're certainly encouraged for innovation in this area for the community. They're very far off, right? It's very hard to evaluate them at this point, so I think it's just a wait and watch situation. So on to the next question, please. Our next question comes from David Nierengarten with Wedbush. Your line is open. Hi. Thanks for taking the question. I had one on reimbursement actually, with the QTCs. Maybe you could help us walk through, you know, kind of the patient flow. So if I'm a sickle cell doctor and I have a patient, and, you know, they wanna, of course, undergo the gene therapy, do I refer the patient to a QTC and the QTC takes essentially on that, you know, financial risk of the, you know, referral? Or, you know, or am I still, I don't wanna say on the hook, but you know what I mean about the CAR-T therapies that had a upfront risk to, some of the doctors in the beginning, and that was a bit of a hurdle for smaller clinics, especially that don't have the working capital. I was just curious if one of the, you know, reasons, of course, for the QTCs was to offset that financial risk or, you know, I mean, how is that plan to work? If you could help us out with that. Thanks. Sure, David. I'll pass that one over to Tom as well. Yeah. Good morning, David. Thank you for the question. First, to address your question on patient flow, patients end up in a lot of different points of the healthcare system, whether it's their primary care physician, a community hematologist, or even potentially an emergency room. The idea for the QTCs is to eventually get them into one of the qualified treatment centers that is approved to administer gene therapy. Keep in mind that we plan to have a qualified treatment center within a close proximity to all patients in the United States or you know, within a high percentage. To answer your question about the financial implications, our strategy is really two-pronged in that we're both working with payers and also working with our QTCs and providers to make sure that not only is lovo-cel covered from a payer perspective but also reimbursed in a timely manner at the provider level. We've also worked with providers now for multiple years coming up with our distribution strategy so that there will be options for them if they do not wanna take on the financial burden. We can handle that through our supply chain. We are confident in the not only coverage but also the reimbursement and then the financial risk, if you will, at the provider level. Okay. Thank you. Our next question comes from Gena Wang with Barclays. Your line is open. Thank you for taking my questions. I wanted to ask one more question on the analytical comparability regarding the CMC path. Just wondering, you did share, you know, some outline with the FDA on certain criteria for the characterization within certain area regarding the comparability. Is there a risk you may miss that criteria? Can you elaborate a little bit more, you know, what exactly that criteria could be, and could there be any risk you could miss that criteria? Gina, thanks for the question. I think we're not gonna elaborate on what those criteria are, but I will pass it to Kasra to comment on the question. Thank you for that question. With regard to risk of meeting analytical comparability, I should point out that the biggest change we made to our process was the suspension change, and we did introduce the suspension in our 206 study. Some patients in 206 have been treated with suspension along with adherent. We have both analytical data and clinical data from the 206 study that de-risks the comparability. We're feeling pretty confident about the comparability as it stands right now. Thank you, Kasra. Next question. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Hey, good morning, and thanks for taking the question. This is Elizabeth on for Salveen. Could you remind us of how you're thinking about preconditioning on the forward and any efforts to potentially develop, you know, gentler preconditioning regimens and when they could come online? Thank you. Hi, Elizabeth. Thanks for the question. I'm gonna pass that over to Rich. Yeah. Thanks, Elizabeth. You know, reduced toxicity conditioning is really important for us and even more important for the patients, of course, because obviously when we use chemotherapy to condition patients, there are adverse events associated with that. It also, in some respects, limits the number of patients who are medically eligible to undergo transplantation. With regard to that, we're actively exploring new methods in order to perform reduced toxicity conditioning, making sure we can clear the bone marrow niche in order to get lovo-cel into the patients again. We're, you know, I think so far, we're not ready to say when we're expecting to go into the clinic yet, but we're working on this very hard. Yeah. Thank you, Rich. Actually, I think at the root of this question is a commercial question as well, so I'll just pass that to Tom. Yeah. Thank you. I just wanted to make a quick comment about the potential. The blockbuster status that I mentioned earlier in the initial 20,000 patients or, you know, north of 20,000 patients does not necessarily depend on reduced toxicity conditioning, that those numbers are based on the current patients in our clinical studies. Thank you, Tom. Okay, next question. Our next question comes from Matthew Luchini with BMO Capital Markets. Your line is open. Hi. Good morning. Thanks for taking the questions and appreciate the update. Was just hoping that you could provide a little bit more perspective on the conversations you've been having as it relates to access and reimbursement. Maybe, you know, whether it's comparing and contrasting a little bit what you've heard from your conversations with government payers versus commercial or more broadly, you know, what you're hearing in terms of pushes and pulls across the different types of payers you've been talking with, that would be great. Thank you. Thanks, Matthew. I'm gonna pass that to Tom. Yeah. Good morning, Matthew. It's an ongoing good question. We've been really working closely with both commercial and government payers over the last three years. It's been an open dialogue, both in terms of early engagement obviously, but education on one-time curative therapies. You know, we uniquely understand, I think, challenges that both payers face, both commercial payers and government payers. We've been working closely with them on innovative payment models that they could easily adapt and would be acceptable to their systems and to their models. We continue to be excited. We've shared some of the market research, but we continue to be excited about the feedback we're getting from payers and about their excitement to be part of gene therapy and part of offering a one-time curative therapy. Thank you, Tom. Next question. As a reminder, to ask a question at this time, please press star then one on your touchtone telephone. Our next question is from Yanan Zhu with Wells Fargo Securities. Your line is open. Great. Thank you for taking my question. I'm wondering, have you had any further discussion or feedback from physicians and patients with regard to the MDS AML cases seen in the studies? I know you have exonerated the involvement of the drug product in those cases, but just wondering, what's the perception from a physician's perspective, for example, and how does the rate that these events occurring in a trial compare with the rate of these kind of leukemogenic events physicians see in their clinical experience? Thank you. Yeah. Great. Let me pass that to Rich, our answer. Yeah. Thanks, Yanan. You know, this is an important question. As you heard from Dr. Smith, there's a lot of excitement about lovo-cel and new therapies in general in patients with sickle cell disease, and we're seeing that across the community. I think the underlying your question is an important point. You know, the way I look at it, first, you know, we have a lot of data. We have, with lentiviral vectors in general, there's been more than 300 patients treated in the US I think when you think about sickle cell disease in particular, one of the key things, we already accept the risks of allogeneic transplant. When you look across the rates of leukemia and myelodysplastic syndrome in patients following allogeneic transplant, in the studies that we've seen, they range anywhere from 0% to 14%, more of them in the 5% range following allogeneic transplant. We've had the two cases of AML, as you pointed out, and that puts us in that range of where you are for allogeneic transplant. That risk is already accepted in the community for treating patients with sickle cell disease. Taking that one step further, the big difference is that following lovo-cel treatment, there is not a risk for graft-versus-host disease or graft failure like you see in some patients with allogeneic transplant. The overall risk of severe events, including MDS, AML, chronic GvHD, and death is much lower in our patients compared to what you've seen for allogeneic transplant. Thank you, Rich. Next question. Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Andrew Obenshain, CEO of bluebird bio. Thank you, Shannon. Thank you all for joining us this morning's call. I wanna reiterate what we shared today, and confirm our upcoming milestones. Our team is laser focused on execution and achieving our milestones for our core three products. We look forward to hearing from the FDA on the submission of our BLA for beti-cel for beta thalassemia in the coming days, and our file for eli-cel is on track for the end of the year. As you heard today, for lovo-cel, we have extraordinary clinical data set and a clear path to BLA submission, and we are laying the groundwork for a robust and scalable commercial launch to meet the demand for the sickle cell community, which has waited far, far too long for a transformative gene therapy. We look forward to sharing with you the latest clinical data for lovo-cel at ASH next month. Again, thank you for joining us. The team is available today for additional follow-up. Please reach out to Courtney for additional time. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.