Good morning, ladies and gentlemen, thank you standing by. Welcome to the bluebird's bio Fourth Quarter and Full Year 2022 Earnings Conference Call. [Operator Instructions] Please note that today's conference may be recorded. .

I will now hand the conference over to your speaker host, Courtney O'Leary of Investor Relations. Please go ahead. .

Good morning, everyone, and thank you for joining today's call. I'm Courtney O'Leary, Investor Relations of 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 expectations regarding our future financial results and financial position, in addition to statements of the company's plans, expectations or intentions regarding regulatory progress and commercialization plans. .

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. .

Andrew Obenshain, our CEO, is going to provide some brief opening remarks and discuss our lovo-cel BLA submission. Then Tom Klima, Chief Commercial and Operating Officer, will highlight positive momentum from our ZYNTEGLO and SKYSONA commercial launches.

And finally, Chris Krawtschuk, our Chief Financial Officer, will provide some color on our finances before opening the call up for Q&A, where the team will be joined by Rich Colvin, Chief Medical Officer. .

With that, I will turn the call over to Andrew. .

Thanks, Courtney, and thank you, everyone, on the line for joining the call this morning. bluebird's vision and mission are stronger than ever. Built on a strong foundation of research and clinical development, today, bluebird is making gene therapy a reality for patients and families in the real world.

And I'm immensely proud of the efforts of our entire company as we continue to lead the way for the gene therapy field, proving the commercial model for ex vivo gene therapy with ZYNTEGLO and SKYSONA, and continue to make meaningful progress towards bringing gene therapies to patients and their families with sickle cell disease in the U.S. .

As Courtney mentioned, Tom and Chris will share updates today on our commercial progress and our financial position. But to start, I will focus my comments on the lovo-cel regulatory path. As noted in our press release this morning, we continue to progress our lovo-cel BLA, but speaking plainly, we will likely miss the Q1 2023 submission goal.

Our file is completely written and ready for submission, but we are awaiting feedback from the FDA on CMC. .

To provide context, I will give a time line of our recent interactions with the FDA. In December, we completed drug products comparability analysis and provide the FDA with a snapshot of comparability data. .

In February, we received feedback and questions from the FDA and request that these responses be provided prior to the submission of the BLA. Our team did incredible work and pulled forward the full CMC module, along with additional information and provided them with the agency in the first week of March. .

We believe that this complete data package supports comparability and addresses the questions asked. Now while there's no set time line for the FDA to respond, the agency has conveyed its commitment to a timely response, and we believe that this could ultimately set the stage for a smooth review.

We anticipate feedback from the FDA within a matter of weeks, and we'll move quickly to expedite our BLA pending the resolution of the comparability questions. And I will reiterate the file is otherwise complete and ready for submission. .

We are grateful to the FDA for the ongoing open dialogue and appreciate the importance of ensuring the agency understands the full content of our analyses.

To take a step back, I'd like to remind everyone of the depth of preparation that has gone into both the manufacturing and the clinical development of lovo-cel and the work that will be reflecting the BLA. .

First, manufacturing. CMC modules are the largest sections in any gene therapy BLA. With that in mind, bluebird has an active and collaborative dialogue with the FDA on comparability over the past several years. We've also incorporated learnings from SKYSONA and ZYNTEGLO into our BLA for lovo-cel. .

Now as a reminder for those newer to the bluebird story, through the course of clinical development for lovo-cel, we made improvements in the manufacturing of our lentiviral vector and of our lovo-cel drug product, including changing manufacturing processes, manufacturing facilities and testing sites.

This included changing from an adherence to a suspension process to ensure that we would meet the patient demand at launch with a robust, scalable and commercially compliant process for the 20,000 patients we believe may be eligible for gene therapy. .

Now some of these changes occurred following the completion of our HGB-206 study, which forms the primary evidence base for safety and efficacy to support the BLA.

Therefore, the industry required that we demonstrate vector and drug products comparability, 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 generated from our clinical trials in our clinical facilities. .

These analysis were completed at the end of last year. We remain extremely confident in the quality of our overall BLA submission package. And as part of that, we may move to our impressive clinical data.

Our clinical data reflects the most robust data available with the longest follow-up across any gene therapy program for sickle cell disease, and it includes more than 50 patients treated and multiple patients followed for more than 6 years. The strength of this package has been reinforced by positive interactions with the FDA. .

The BLA submission will be based on efficacy results from 36 patients in the HGB-206 Group C cohort and will include a median of 32 months of follow-up and more than 4.5 years of follow-up for some patients. We anticipate that the BLA submission will also include efficacy results from 2 patients with 18 months of follow-up in the HGB-210 study. .

We plan to request priority review for patients 12 and older with the history of vaso-occlusive events. Importantly, at this time, we are not forecasting any change to our commercial plans for lovo-cel and are continuing to anticipate an early 2024 launch.

And we are really looking forward with -- to delivering on the promise of gene therapy for sickle cell patients who have been waiting for therapies like this. .

As Tom will discuss, the foundation that we are building today to bring ZYNTEGLO to patients will directly translate into our ability to bring lovo-cel to patients. We have the same treating positions, the same QTC network and the same payer relationships.

Bluebird has over a year head start launching a gene therapy in inherited hemoglobin disorders versus any other gene therapy program. .

And with that, I will turn it over to Tom to highlight how our launches are progressing. .

ZYNTEGLO and SKYSONA. There's a lot of attention and noise in gene therapy these days, but the reality is that bluebird, we are living it every day and bringing these important, onetime treatments to patients. .

During the recent field visit, I received feedback from health care professionals in our QTCs. They praised bluebird for our continued partnership and for leading the way with our deep expertise and through transparency. They reinforce that our trusted partnership over the years will be an important differentiator. .

As a reminder, our commercial strategy is built on 3 key pillars, which are fundamental to success in gene therapy launches. First, patients and their families are at the center of everything we do, and they are the ultimate decision-maker.

Our continued engagement over the past decade and our ongoing education about gene therapy, are critical for adoption. .

Second and unique to ex vivo gene therapies, we're building a network of qualified treatment centers or QTCs where the cell collection and infusion of our therapies takes place. These centers of excellence are both part of our supply chain, but there are also ambassadors for patient care and ultimately for our therapies. .

And finally, access and reimbursement, an area where we have innovated as pricing and securing coverage for a one-time therapy is certainly not the same as pricing of chronic therapy. Importantly, we are seeing success in all 3 areas since launch with momentum continuing to build. .

For ZYNTEGLO, we are seeing significant patient demand and uptake highlighting the tremendous unmet need and interest in gene therapy from patients with beta thalassemia. To date, there have been 5 patient starts or cell collections for patients with beta thalassemia coming from our early Wave 1 QTCs.

This momentum will continue to build as we grow our QTC network. And notably, as launch progresses, we are already advancing our plans to expand our manufacturing capacity to meet growing projected demand. .

On the reimbursement front, we're pleased to report that things continue to go very well. On average, prior authorization is taking only 2 weeks, a strong indicator that payers recognize the value of ZYNTEGLO in a rare disease with significant unmet medical need. Most important, we continue to see zero ultimate denials. .

Switching to QTCs. We have expanded our QTC network as planned with 12 centers activated to date, representing a mix of both pediatric and adult centers. Approximately 30 additional QTCs are in the onboarding stage or MSA negotiation phase and the company remains on track to scale to between 40 and 50 QTCs by the end of 2023.

This progress is because of our preparation and is also a signal of patient interest and enthusiasm among physicians for ex vivo LVV gene therapy. .

Importantly, as Andrew mentioned, the efforts we're making with ZYNTEGLO will directly translate to the potential launch of lovo-cel for sickle cell disease in 3 key ways. First, and very simply, the treating physicians are the same. Second, the bluebird QTC network will be the same.

This means that from an operational standpoint, our expectation is that we will reduce the lead time for QTC activation for months to weeks because of the synergies. We're really doing the groundwork now so that we will be ready to begin treating patients shortly after approval. .

And lastly, with payers, we're already being recognized as leading the way with our approach to value demonstration and innovation with our outcomes-based agreements, and this established credibility will carry forward.

We will continue to provide updates on key metrics from the Zynteglo launch, including a number of patient starts as launch progresses. We believe the most important metric for you to keep an eye on is the number of patient starts. .

For SKYSONA, cell collection has been completed for 2 patients. And on March 16, the first commercial infusion was completed at Boston Children's Hospital. I cannot overstate what an incredible moment this was for this patient and his family for the clinicians and researchers and for the entire ALD community. .

CALD is a devastating disease, and this was a milestone celebrated by all those who have advocated, invested and fought for treatment options for many, many years. It is difficult to summarize the passion and the pride we all have in being able to deliver SKYSONA to that young boy and his family. .

In conclusion, I'm extremely proud of the progress and dedication of our team and how we're leading the way as a commercial gene therapy company. .

With that, I'll turn it over to Chris to talk through the financials. .

Thanks, Tom, and good morning, everyone. It's gratifying to be speaking with you publicly as bluebird's CFO for the first time since I joined the company back in November of 2022. We now stand in 2023 in the strongest financial position Bluebird has had, since we emerged as a dedicated gene therapy company in November of 2021.

I'm immensely proud of the work our bluebird team has done to get us to this point and over the past few months. .

During the 5 months beginning November of 2022, we were able to raise $326 million in net proceeds from the sale of our 2 PRVs and our equity offering. These actions extended our cash runway into the fourth quarter of 2024, when including our restricted cash.

Retiring our near-term balance sheet risk has been a top priority for bluebird, and I'm pleased we're able to provide financing for over 50% of our market cap with just 17% dilution. .

We will continue to remain opportunistic and looking at options to extend that cash runway even further.

We remain on track with our full year 2023 cash burn guidance in the range of $270 million to $300 million and continue to prudently deploy capital as we launch our first -- I'm sorry, as we launch our 2 first-in-class gene therapy and prepare when lovo-cel is approved and available for patients. .

As a reminder, it's premature to provide revenue and top line guidance at this point in our launches. The company anticipates its first commercial revenue will report Q1 results in May. .

Lastly, I'll touch briefly on the Silicon Valley Bank and its impact to Bluebird. Following the bank collapse earlier this month, we were pleased to see the FDIC announcement and that the impact appears to be minimal for the industry.

For bluebird, we remain in a strong financial position and have diverse banking relationships with controls in place for continuous monitoring of the health of these organizations. .

However, of note, SVB does hold approximately $43 million in restricted cash for bluebird, primarily related to the collateralized letter of credit in connection with the execution of our sublease for the 50 Binney Street lease in Cambridge, Massachusetts.

We continue to work on releasing the restricted cash, and we'll provide updates as and when they become available. .

With that, I'll turn it back to Andrew. .

Thanks, Chris, and thanks, Tom, for walking us through those updates. It is a really exciting time at Bluebird. We are in the midst of 2 first-in-class launches, showing up for patients with CALD and with beta thalassemia, and they're so close to bringing our gene therapy to individuals living with sickle cell disease. .

And with that, I'd like to invite Richard Colvin to join me, Chris and Tom for questions.

Operator?.

[Operator Instructions] And our first question coming from the line of Jack Allen with Baird. .

Great. And congratulations on the progress over the course of the quarter. I guess my first question is around the lovo-cel updates. .

Can you provide some context around the number of patients that were treated with the suspension process?.

And then just to clarify, is the FDA asking for additional comparability data? Or is this a discussion of existing data?.

And then finally, any analogous situations that you point towards as it relates to these comments?.

Jack, thanks for the questions. So on the last one, I can't report to any analogous ones in terms of -- because I think it's the -- there's been a CMC with gene therapy in general, has been something that the FDA has been focused on. There are plenty of other examples of people who have switched manufacturing plants et cetera.

But I might go into details of other analogous here. The -- your question regarding the -- sorry, what was your second question. Can you repeat that, Jack -- that was -- you asked... .

The second question was about -- just to clarify, is FDA asking for additional data here? Or is it a discussion of existing data as it relates to responses?.

Well, let me just walk through the time line again. We provide a snapshot of our data. So a thinner package of our data to the FDA in January. They came back with questions about that data and request for more information. We provided that in early March for them to review..

And then the question about -- and we're not getting into details right now on the package about how many suspension patients were versus hearing on the details of that package right now. .

And our next question coming from the line Yaron Werber from Cowen. .

This is Brendan on for Yaron.

I guess just really quickly, looking ahead to potential lovo-cel launch, what can you kind of tell? I know it's a little bit early here, but really based on your conversations around SKYSONA and ZYNTEGLO now, what do you kind of think -- what can you tell us about how you're thinking about pricing and reimbursement? And maybe how those conversations for the first 2 drugs have kind of guided your thinking over the recent months.

.

Yes, I'd like to hand that over to Tom to respond. .

Yes, thank you for the question. We've been obviously working on the potential price for lovo-cel for quite some time.

Clearly, we will take the same data-driven approach to assessing the value of lovo-cel that we took to approach the value of ZYNTEGLO and SKYSONA, taking into consideration, obviously, the positive clinical outcomes, quality of life improvements, health system cost savings and potential societal impact of patients and families. .

Again, we'll go through the process. It's probably a little bit too early to give you much more detail on that. But we -- I will say that we are already working with payers and talking to them about what an outcomes-based agreement might look like. .

Keep in mind that with ZYNTEGLO, the outcomes-based agreement was pretty straightforward. And with a larger population in sickle cell disease, we'll come up with something different that meets the needs of that population. .

And our next question coming from the line of Jason Gerberry with Bank of America. .

Just a follow-up, just one on the regulatory point. So there's no additional CMC work. It's purely just kind of waiting for a response from the FDA at this point. And then one commercial question. .

Just within the context of sickle cell, how would you envision centers sort of embracing and adopting 2 competing gene therapies if they're presumably rolling out around the same time?.

Just kind of curious if that presents anything unique? And if centers might only choose one? Any color in terms of how you're thinking about that process evolving?.

Jason, I'll take the first part of that question, hand the second part over to Tom. So in terms of -- we believe that we've submitted a complete data package at this point. We're confident in what we've put together. It's in the hands of the FDA right now, and we are waiting for their response to make sure that they agree with that.

And then I'll hand it over to Tom for the... .

Yes. Jason, I think it's a good question. We -- I think the first important thing to point out is that we're actively treating patients today in these QTCs for beta thalassemia and we'll have over a year head start. And we believe based on feedback that, that will translate into an advantage for our therapies with the experience and synergies.

We don't believe that most centers will be exclusive to one therapy or the other. .

If you look at other markets like the CAR T market, for example, most centers of excellence like we'll like to offer all available -- especially all available innovative therapies. So we wouldn't anticipate centers offering just one of the therapies. .

And our next question coming from the line of Yanan Zhu with Wells Fargo. .

So first on the regulatory process for lovo-cel.

I was wondering what questions or what type of questions did FDA raise if you have any additional color on that?.

We're not going to get into the details of the questions right now to say. They did ask some questions and ask for some more data that we have -- we believe we've fully responded to those questions and submitted the data that we have. So we submitted, it's really the full CMC package from the BLA that we pulled forward plus additional data.

So it's a very robust package that we submitted. .

Got it. Got it. And then on the ZYNTEGLO launch, a couple of questions here. How many patients have verified their benefit or -- rather have gotten prior authorization at this point.

And with regard to the 5 patient starts, do you still estimate 70 to 90 days of manufacturing time? And any estimate on when the first infusion for ZYNTEGLO might occur?.

So I'm going to pass that over to Tom. .

Yes. We really are pleased with how the launch is going, and we continue to see consistent volume of patients who are initiating benefits verification and moving through to the prior authorization phase. We at launch provided that as a metric because it was really the only thing that we had that was the indicator of demand.

We've moved now to focusing on the number of patient starts. So those that have moved through that process and actually started therapy with the cell collection process. .

So we aren't providing any updates. I will just say that we feel very strong about how things are going, and that number continues to increase and be steady. With regard to the 5 patients, we did report this morning that the 1 patient was infused with SKYSONA at Boston Children's.

We reported that one, because that was publicized by Boston Children's, but we're not providing quarter-by-quarter guidance on how many patients are being infused. .

Yes. And then, Tom, he asked question about the manufacturing time as well. We still believe that's 70 to 90 days. .

That's correct. For ZYNTEGLO it's 79 days. And for SKYSONA, it's a little bit less around 55 to 60 days. .

I see. Got it. That's helpful. And maybe lastly, the label -- potential label you're working towards with the lovo-cel submission. I think you mentioned this is a patient greater than 12 years of age. But I guess how -- I think is it -- are there 2 patients with this age range, 12 to 18 that's in the package.

And in general, how confident you are that you could get a label that go down to that age of 12 years once you submit the lovo-cel NDA -- BLA. .

Yes. So there's more than 2 patients in there. We're not going to get into the actual split of numbers right here, but we are submitting for the 12 and over. We have studied this patient group, there's clinical benefit for this group as well.

Rich, do you want to make any more comments to that?.

No. Thanks, Andrew. No. We have just what Andrew said, there have been more than 2 patients, and we have studied them in Study 206 and also in 210. .

Right. Got it. Got it. Yes. So I only got the 210 number. Yes, got it. That's helpful. .

And our next question coming from the line of Sami Corwin with William Blair. .

I know previously, you've stated that there are some patients who will initiate benefits verification for ZYNTEGLO or received prior authorization, but will not proceed with treatment. And I guess I was just curious, if you're collecting any data with that regard as to reasons patients are proceeding with treatment. .

And then just a second one on ZYNTEGLO.

With your current number of QTCs in place, how many patients are you able to reach with the current QTCs in place? And how many will you be able to reach if you hit your goal 40 to 50 centers by the end of the year?.

Go ahead, Tom. .

Yes, great question. So we do collect information on patients who start the -- both the benefits verification and prior authorization part of the process. And should they choose not to go forward with therapy, we do collect and monitor the different reasons why.

I won't get into a comprehensive list today, but it could be something as simple as they're finding out that a QTC is going to be in their state soon, so they want to wait until a QTC is closer to where they live or they want to wait for to get through an event in their life like a play or a school graduation or something like that. .

So we aren't seeing a lot of patients completely fall out of the funnel, so to speak, but we're seeing more kind of continuation type of reasons, at least in the early phase.

And the second -- what's the second part of your question?.

How many patients are able to reach with your current QTCs in place and how many you'll be able to reach if you hit your goal of 40 to 50 centers?.

Yes. So of the 1,500 patients in the U.S. who have -- QTC -- our initial Wave 1 QTC network we thought we could reach about 50 patients. That was with our first 5 QTCs. We're now at 12 QTCs. And ultimately, our goal is to get to between 40 and 50 QTCs, which would give us access to the roughly 850 patients that we feel fall within our label.

So that's the ultimate goal by the end of the year. .

And our next question coming from the line of Mani Foroohar with SVB Securities. .

This is Jenny on for Mani. We were just wondering if you could provide any clarity on differences between beta thal, sickle cell disease and CALD on time between new patient start forms and revenue recognition. .

And if so, what are the key variables that would drive any differences going forward?.

Yes, that's -- so let me turn that over to Tom just to talk about the kind of the lovo-cel, the ZYNTEGLO and the SKYSONA manufacturing times just from the time of initiative from the time of a new patient being getting a start form until we can go to the drop back and maybe I'll hand it over to Chris just to talk about revenue recognition. .

Yes. So we're intentionally building in a lot of synergies so that we both maximize our current launches but set ourselves up for success for lovo-cel. So the -- a lot of the operational stuff that we're going through now becomes very simple when we get to lovo-cel.

So we feel that we will be able to reduce kind of the QTC onboarding time when we get to lovo-cel 2 weeks. ..

The turnaround time from the time we collect cells until the time we are ready to shift those cells back to QTC is between 70 to 90 days on average for ZYNTEGLO and 55 to 60 days for SKYSONA. The majority of that time is based on the testing and the release -- the testing assays and the release that we do after we manufacture.

We believe the time for lovo-cel will be roughly the same, but we don't have that finalized yet. So stay tuned for that one. .

But operationally, how they enroll for treatment is going to be very much the same with the same treating physicians. So keep in mind, the physicians now are getting their experience so that as we get to sickle cell disease, they already have those experiences and the learnings from the ZYNTEGLO and SKYSONA launch. .

And Chris, do you want to talk about revenue?.

Sure. Thanks, Tom. And with respect to revenue recognition, we recognize revenue on bluebird's financial statements in the patients infused. .

And our next question coming from the line of Dane Leone from Raymond James. .

Sorry to rehash it again. But obviously, there's just -- with some of the history of the CMC discussion that the bluebird team has had with the FDA specifically.

Can you just kind of break it down really simply why this is not a situation of years past? And from a technical perspective, really, the differences here, what you have to resolve in your communications versus some of the hiccups that you've experienced before that you actually had to take corrective action on before having an accepted filing. .

Dane, good question. The last couple of years, the entire gene therapy space has gone through a learning period, right? And Bluebird, we -- as innovators, we've always been on the first to experience the pain. And you've seen that over the last couple of years ago. .

And both the FDA and the industry, the gene therapy industry have matured in terms of mutual understanding what is required for CMC. And so over the last 2 years, we have been in constant dialogue with the FDA about comparability and how to approach it.

And the conversations over the last couple of years have been focused on what we would need to do, the recipe that we need to follow how we do it. The conversation today is of the content of the analysis and what we submitted. So that's the difference. .

So just to be perfectly clear, and again, sorry to rehash it. There's no suggestion or thought that you would need to run any additional assays or do assay work there's a request for additional information that you have in-house. .

So I cannot predict the FDA, okay. As -- but as closer we are to them, one of the things I will never get on conference call is, say is the FDA will not come back and ask for more data. I just can't, right? I think that's -- but we are extremely confident in the package that we put together.

Really the entire BLA CMC package plus additional information. We've been working on this for years now, right? We think we've been trying to see around every corner we can. So I think what you're hearing is on the bluebird side, we have a lot of confidence. I cannot speak for the FDA. .

And our next question coming from the line of Gena Wang with Barclays. .

And this is [ Shao Jiong ] on for Gena. Two questions from us. The first question is about the -- patient infused with ZYNTEGLO. So if I remember correctly, your first patient cell collection for ZYNTEGLO was earlier than SKYSONA. So if you think about the time difference from cell collection to infusion is about 15 to maybe 20, 30 days.

Should we assume the first patient have been infused with ZYNTEGLO or any other factors in play about the time line here?.

I'm going to pass that to Tom to respond. .

Yes. So we don't plan on updating month-by-month or quarter-by-quarter on number of infusions. Keep in mind that the part we can control is the vein-to-vein time or the time from apheresis to the time we ship the cells back. We cannot control the time after QTC gets the cells back when they might infuse that.

We did talk about the SKYSONA one because it was made public by Boston Children's Hospital. They actually publicized on it quite a bit and announced it at a meeting. We had committed to being on track to recognize our first infusion commercially in Q1, and we feel happy that we achieved that.

But yes, you're right in that the main difference is that the ZYNTEGLO lead time is 70 to 90 days on average and SKYSONA is a little bit shorter. So that's the one variable. And keep in mind that SKYSONA, the boys with SKYSONA progressed rapidly. So there's much more of an urgency to treat with SKYSONA. .

If I may ask the second question. So my understanding is bluebird will get paid directly from QTC.

So how much out of the data price to payment they can get for example, so what did the payer agreed to pay to the QTC for $2.8 million per patient and the QTC want to make some profit out of it, what will be the discount to bluebird? Will discount be the same for all QTCs under the master service agreement?.

Tom, go ahead. .

Yes. If I'm understanding your question correctly, bluebird just receives the price of the drug. QTCs through the -- as they go through the prior authorization process or securing the payers' commitment to pay for not only the drug but also the cost of the procedure and then they negotiate a case rate for themselves.

So they negotiate usually something around the drug and something around the procedure of the transplant. But that is very private information. QTCs don't share that information with us and payers don't show that information with us. So that's a bit of an unknown to us, but they do that on the side for therapies like this. .

And our next question coming from the line of Luca Issi from RBC Capital. .

Great. This is Lisa on for Luca. Just a couple on ZYNTEGLO here. Just wondering if you can add some more color on the 5 patients who had cell collections. .

Did these collections occur at more than 1 of the 12 QTCs that are currently online? And what is the -- and also as well, if you could add more color on the growing patient demand that you are seeing? Is this coming from a handful of doctors in a localized geography? Or is this coming from more broadly throughout the U.S.?.

Yes. Sure. Good questions. Yes, the patient, we won't get into center by center, but the 5 patients that we reported are coming from multiple centers from our early Wave 1 QTCs. And that's why we're confident as we bring up more QTCs, we continue to see demand in each QTC that we bring on board.

So the growing demand is coming from not only the existing QTCs that have already started treating patients. But as we bring on each new QTC, they have patients to be treated. So the answer to that is both. .

And keep in mind, our plan was to start with the 5 QTCs and roughly, we thought about 50 patients at launch and then to rapidly grow that to between 40 and 50 QTCs by the end of the year. That also, I think, maximizes our opportunity and sets us up for success with ZYNTEGLO, but also really lays the foundation for lovo-cel and sickle cell disease. .

That's helpful. And then just maybe a quick one on sickle cell.

Are there plans to expand beyond the 40 to 50 QTC centers planned already for 2023 when sickle cell potentially launches in 2024?.

Yes, it's a good question. Right now, our goal is to get to between 40 and 50 QTCs this year by the end '23. What we're learning and what we know about patients in both -- with both beta-thalassemia and with sickle cell disease is that some patients are willing to travel, but some patients would prefer to get treated closer to their home. .

Our goal ultimately will be to bring our treatments to patients so that they don't have to travel very far for treatment. But we're not going to say what we're growing to beyond the 40 to 50 right now. It's fair to assume that we'll probably end up with higher than 50, but we're not commenting on how many at this time. .

And our next question coming from the line of Salveen Richter with Goldman Sachs. .

This is [Anabel] on for Salveen. We have 2 questions. The first one on lovo-cel.

In light of this delay, how are you thinking about the competitive positioning of lovo-cel?.

And then on ZYNTEGLO, how much overlap do you think there would be between the QTC that you're going to establish this year and then those that would be needed for sickle cell? And then just quickly on the ex U.S. opportunity.

When do you think you would be ready to think about that?.

I'll just take the last one first and hand it to Tom. On the ex U.S., we are focused on the U.S. only right now. We got this -- we are getting the therapies launched, getting the therapy to patients in the U.S. It's not on our radar screen for ex U.S. at the moment. Tom, go ahead. .

Yes, sure. I'm going to start with your QTC question first. Our QTC -- the way we designed our QTC network was to -- the QTCs that have expertise in cell and gene therapy, but also treat both beta thalassemia and sickle cell disease. .

Over index those that have high populations of beta-thalassemia first, and then we're going to grow to QTCs that have higher concentrations of the patients with sickle cell disease. But the simple answer is we believe that 100% of our network will be both ZYNTEGLO and SKYSONA patients -- I'm sorry, centers. .

When you think about the competition in your competitive question, I think I said this earlier, but I think the first and foremost thing to point out is that we're already in these treatment centers.

And so even with the slight shift in our time line, we believe that we have a competitive advantage by being there first and we'll be there first for over a year. And then as we've done market research over the years, we've seen a slight advantage for lovo-cel.

So we feel very confident that the shift in time line is not going to impact either of those things. .

And our next question coming from the line of Matthew Harrison with Morgan Stanley. .

This is [indiscernible] on for Matthew. So can you comment on the cadence of the patient starts.

So what happens after patient starts, like how long it takes to -- for cell collection? And do you expect all the patient starts to be converted into dosed patients? In other words, should we expect some patients maybe not going into dosing after starts?.

Go ahead, Tom. .

Yes. As far as cadence, just to give you a high-level review, a patient will come in for obviously a consultation as they start the benefits verification and prior authorization process. ..

As I noted on the call, the prior authorization process is taking about 2 weeks on average, which is great news the payers recognize the value of ZYNTEGLO and SKYSONA. And then obviously, they'll go through their cell collection and then go back home. .

This -- as I mentioned, cell collection to when we ship the cells back is between 70 and 90 days and then it's really up to the patient and QTC to decide when they come back in for their infusion and their treatment. .

That part is a little bit less clear to us right now, and we will wait until we treat a lot more patients before we kind of give thoughts on how long that might take on average.

But the -- your last question was how many patients that -- we're focusing in right now on starts because we believe that once the patient goes through the apheresis process, they're committed to therapy. So we don't anticipate a lot of patients to pull out of therapy or fall out of the funnel once they go through the cell collection.

But that's why we're focusing on patient starts. .

And I'm showing no further questions at this time. I would now like to turn the call back over to Mr. Andrew Obenshain, for any closing remarks. .

Thank you very much, and thank you, everyone, for joining this morning. I just wanted to reiterate how proud I am of our team in terms of what we've done over the last several years to bring 2 therapies to patients and getting close to 1/3 and completing this BLA and actually pulling the workflow over in a timely manner.

So -- and we -- it is a time where bluebird is finally delivering on the mission it had for over a decade. So really, really proud of the team. So thank you, everyone. .

Ladies and gentlemen, that does conclude the conference for today. Thank you for your participation. You may now disconnect..