bluebird bio Inc (BLUE) 2020 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the bluebird bio First Quarter 2020 Earnings Conference Call. (Operator Instructions)

I would now like to hand the conference over to Ingrid Goldberg. Thank you. Please go ahead.

Thank you, and good morning, everyone. This is Ingrid Goldberg, Investor Relations at bluebird bio, and welcome to today's conference call to discuss our quarterly earnings and the business update. I'm joined today by several members of the bluebird management team.

The format of today's call will be opening remarks from Nick, a sickle cell disease regulatory update from Dave, and we will complete the call with highlights from our revised operating plan from Chip. We will then turn to your questions.

Before we begin, I would like to remind everyone that our discussion today includes forward-looking statements under the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on our current expectations and assumptions that are subject to risks and uncertainties, and actual results may differ materially from those expressed today due to a variety of factors. Additional information concerning these risk factors are in our filings with the SEC and available on the Investors section of our website at www.bluebirdbio.com.

As a reminder, while we may elect to update forward-looking statements in the future, we do not undertake any obligation to update forward-looking statements even if our expectations change, except as required by law. You should not rely on these forward-looking statements as representing our expectations as of any date subsequent to today.

With that, I will now turn the call over to Nick.

Thank you, Ingrid. As we've always done, we start by reminding us all why we do what we do, the why. Our industry faces very tough odds, and it is easy to lose the narrative or get discouraged by the never-ending battle to find medicines that matter. Our belief is that the odds are best overcome by deeply caring and making it personal. The walls don't seem as tall or as thick or as painful to run into if we focus and keep our focus on the why.

The COVID-19 pandemic has reminded us all how fragile life can be and also how important it is to come together in times of need. I'm personally proud of how our industry responded to the crisis. And hopefully soon, we'll be able to deliver medicines to the front lines as well as perhaps serve to reestablish some of the lost public and political trust of our industry.

Specific to bluebird, I'm extremely pleased to witness how the team has responded to the crisis, to not only scramble to ensure business continuity and safety of our employees, but also to work tirelessly with our clinical sites, manufacturing partners and everyone necessary to ensure we do right by our patients and their families. Inside and outside the company, we've seen folks stepping up in all sorts of ways with truly inspirational and very human leadership. The positivity, passion and focus on the silver lining is just amazing.

The impact of the pandemic on bluebird is not yet fully known, and we intend to remain vigilant as we continue to navigate the best we can until normal operations resume. With that as context, I'm all the more excited to share the tremendous progress in not only developing a revised operating plan, but also in advancing our key development programs.

The progress has been significant across many fronts, further solidifying the fundamentals of bluebird's vision for patients and our operational strength to execute. First, we recently hit -- first, let me cover several recent critical milestones. With our partners at BMS, we shared exciting top line results for our KarMMa study back in December, and in Q1 of this year, submitted the U.S. BLA for ide-cel for the treatment of late-stage multiple myeloma. Stay tuned for an updated data presentation at this year's virtual ASCO meeting and for a data summary press release this coming Wednesday, May 13, once the ASCO embargo lifts.

On the sickle cell disease front, we're happy to share that we have reached general alignment with the FDA on an accelerated approval path for LentiGlobin in sickle cell disease with plans to file for approval in the second half of 2021. We plan to share the latest data reviewed with the FDA at the upcoming EHA meeting in mid-June.

Overall, 2021 is on track to deliver several major milestones, including ZYNTEGLO commercial ramp in Europe; U.S. approval and launch of ide-cel; and the U.S. filings of Lenti-D for CALD, LentiGlobin in thalassemia and now, LentiGlobin in sickle cell.

Second, as promised on our March 26 update call, we have made significant progress on the operational front to reflect the changes to our plans and the unknowns brought on by the COVID-19 pandemic. Notably, we have optimized our relationship with BMS to best serve ide-cel and monetize our ex U.S. rights for $200 million to add to our operational resources and flexibility. In addition, with the help of the entire bluebird flock, we have tuned our plan to reflect new realities, removing over $500 million from our operating plan through mid-2022.

Finally, as Chip will share in more detail, the revised plan extends our runway into 2022 while keeping our core 4 late-stage programs and pipeline promise intact.

The operating budget is important, but as many of you know, it does not tell the whole story as it can be disastrous if not done with care and transparency. Stressful times and deep cuts -- deep budget cuts and program changes can tear apart a company's culture and greatly diminish long-term viability as core values and vision get replaced with shortsighted objectives that can kill innovation and organizational drive to succeed. I'm very happy to report this is not the case at blue. We are keeping our eyes on the horizon and what will get us the best chance to positively change the stories for the patients we aim to serve. As I often talk about, over the last 10 years, we've learned through experience to love the bumps and use them as a chance to get stronger. I'm fired up more than ever seeing the anti-fragile nature of our people reach a new level despite the unprecedented conditions. Although not over yet, we strongly believe we will not only come through this time healthy, but actually the stronger for it.

Our fundamentals are even more sound as we recode our way to delivering transformative products, and our operating plan is now more focused and balanced as we mature into a fully integrated biotech company, delivering over the coming years on the promise of hope. In short, our blue mojo is shining bright with one charge, deliver patients the bluebird day they so desperately deserve.

With that, I'll hand it over to Dave for some program details, and then we'll go on to Chip for the operational plan details. Dave?

Thanks, Nick, and good morning, everyone. To provide some context for this regulatory update and as a refresher as we approach EHA in June, I would like to remind you of the high point of the clinical data with LentiGlobin for sickle cell disease that we presented at ASH last year.

Vaso-occlusive crises represent the quintessential clinical manifestation of sickle cell disease. These painful and life-threatening crises may completely derail the lives of patients with sickle cell disease, often leading to hospitalization, progressive, irreversible organ damage and increased morbidity and mortality. These crises, as well as stroke, are the most clinically meaningful endpoints for patients and clinicians.

On this data figure from ASH, capturing the frequency of vaso-occlusive crises and acute chest syndrome in patients from study HGB-206 Group C, each bar represents a patient in the study who had at least 6 months follow-up. On the left is the pretreatment time period with each all too frequent red diamond representing an event. The right side of the figure shows the follow-up period after LentiGlobin infusion. And remarkably, we see a 99% reduction in crises. These data truly communicate the transformative potential of LentiGlobin gene therapy. The impressive magnitude of the treatment effect has recently enabled a positive and productive Type B meeting with the FDA and that has allowed us to revise and accelerate the development path for this program. As Nick mentioned, we plan on providing an update of the 206 study results at EHA.

Next slide. Our prior development plan to support approval consisted of the Phase I/II 206 study and the Phase III HGB-210 study. Our initial goal with 206 was to establish the correlation between hemoglobin-based outcomes, captured as a globin response primary endpoint, and the occurrence of vaso-occlusive events, which was the key secondary endpoint. This approach was intended to support accelerated approval based on observing favorable interim results for globin response in HGB-210.

On the basis of the 206 data, our recent discussion with the FDA has provided alignment on a new path to a BLA, which is shown on this slide. In agreement with the FDA, we have updated the primary endpoint of the 206 study to be complete resolution of severe vaso-occlusive events, which reflects the most clinically meaningful outcome achievable for patients in this study.

With this change, we are planning to seek accelerated approval based on a subset of patients in Group C of the 206 study. The globin response endpoint will shift to being the key secondary endpoint. While we are not specifying the number of patients that will be necessary for the submission, we anticipate that we have already treated sufficient patients in Group C to demonstrate efficacy to support our filing with additional follow-up of at least 18 months after infusion. For the purpose of supporting an accelerated approval, the initial data submitted on complete resolution of severe vaso-occlusive events will serve as an intermediate clinical endpoint to be subsequently confirmed with longer follow-up. Given the clinical data package we have outlined, we anticipate being able to submit our U.S. BLA in the second half of 2021.

In parallel, we will continue to move forward with the Phase III HGB-210 study which will serve as a post-approval confirmatory study. This study will allow us to evaluate pediatric patients with sickle cell disease, in addition to treating patients in the EU and gaining additional experience with suspension lentiviral vector. These 2 studies together will build a comprehensive clinical data set that will enable us to engage in additional regulatory dialogues, potentially enabling future label and geographic expansion and serve as the basis for full approval.

Next slide. As Nick mentioned, we have made meaningful progress not only for sickle cell disease, but across our late-stage clinical programs. We, in partnership with Bristol-Myers Squibb, recently submitted the U.S. BLA for ide-cel in patients with relapsed/refractory multiple myeloma. As we prepare to commercialize, we have amended our collaboration, important progress that Chip will discuss in more detail.

We are also looking forward to presenting data from the pivotal KarMMa study as part of this year's virtual ASCO meeting. Our CRB-402 Phase I/II study of bb21217 in patients with relapsed/refractory multiple myeloma remains active, but enrollment has slowed due to COVID-19.

Despite the global challenges from COVID-19, which, for our patients with TDT, has highlighted the risk of being tethered to frequent blood transfusions, we have been pleased with the progress made by our bluebirds and external partners for ZYNTEGLO in Europe in consenting and preparing patients for treatment in Germany as well as for gaining access and reimbursement in additional EU countries. We look forward to providing updates at EHA for our ongoing HGB-207 and 212 pivotal studies.

And finally, we are pleased that Lenti-D for CALD remains on track for planned regulatory filings in the EU this year and in the U.S. next year, and we anticipate providing updated clinical data for Lenti-D at a medical meeting later this year.

And with that, I'll turn the call over to Chip.

Thanks, Dave. Good morning, everyone. I'm pleased to outline our revised operating plan and updated financial guidance on today's call.

The last 2 months have been a time of unprecedented change with the COVID pandemic and the profound impact to the economic and capital markets outlook. Despite these dramatic changes to the macro environment, the fundamentals of our business remain strong, and so we realized that we needed to find a way to deliver on the 2022 vision in a streamlined and capital-efficient way. As we continued to prove out the transformative patient impact of our products, we are seeking to balance our commitment to cutting-edge innovation with a plan that moves us forward towards financial and operational sustainability.

Our goals in this plan are fourfold: number one, deliver the core 4 to patients in the commercial setting by 2022; second, continue to innovate by advancing the most promising components of the pipeline and platform technologies; third, scale and grow the business at a more balanced and sustainable rate; and fourth, secure nondilutive funding and extend financial runway. As you heard at the top from Nick, we were successful against all of these goals.

Moving on to Slide 9. We can go deeper on the revised ide-cel collaboration with BMS. This was more than simply a financial transaction, and there are a broader set of strategic takeaways that are good for the program, good for patients and good for BMS and bluebird.

To recap terms of the revised collaboration, over time, bluebird will transition vector manufacturing to -- responsibilities to BMS for the ex U.S. manufacturing. bluebird will continue to manufacture vectors to support the U.S. market. And BMS is paying bluebird $200 million in exchange to our future rights to milestones and royalties related to ide-cel and bb21217 outside the United States.

We are very pleased with the revived collaboration for a number of reasons. First, we have operational alignment in the U.S. and ex U.S. geographies. We've secured $200 million in nondilutive funding for the company at a critical time. And most importantly, we have a shared commitment with BMS to ide-cel, and both sides are investing aggressively to deliver for patients. As you heard from Nick, we are excited to share the full KarMMa data set at the upcoming ASCO conference later this month.

Moving on to Slide 10, I'll highlight the details of our revised operating plan. On the left-hand side of the page, you see the non-negotiables in terms of what had to be resourced and funded in our plan. It starts with the core 4 programs. And here, we're seeking regulatory approval and commercial launch in the U.S. and Europe by 2022.

Moving on, the core 4 doesn't happen without manufacturing and here, we are seeking to secure the supply chain for our pending commercial launch and making the transition to suspension lentiviral vector manufacturing. This is critical from both the cost of goods perspective and a capacity perspective.

Research is a critical part of the revised operating plan, and we are prioritizing support of the core 4, expansion of core 4 potential through technologies like reduced toxicity conditioning, cryopreserved apheresis and suspension LBD and the promising preclinical programs that could be in the clinic in the next 1 to 2 years.

And last, but certainly not least, 2 of our most important assets, people and culture. And this plan supports continued investment there and keeping bluebird blue in all the ways that people have come to know.

On the right-hand side of the page, you can see where we're able to prioritize and drive savings versus the prior plan. This includes facilities, taking actions to reduce our facility footprint and fixed cost overhead; deferred and delayed SG&A build-out, which is more in line with the commercial timing and forecast; label expanding studies, most notably, HGB-211, which was our stroke study in sickle, on pause for the time being; and finally, on the research side, we have been through a process of prioritization of preclinical programs. With this revised operating plan, we have cash runway into 2022, and we're well positioned to create value for all stakeholders.

In conclusion, I wanted to be clear that we are committed to our long-term financial sustainability while balancing the innovative side of our business that got us to where we are today. Happy to answer any questions in the Q&A. But for now, we'll turn it back to Nick.

Thanks, Chip. It's a lot to digest, but we feel it's exciting and important progress towards launching our first 4 programs, optimizing our business for the path forward and doing so without cutting bone, as we say, that won't grow back, preserving what we call R&D with a soul.

In making these updates, we've set ourselves up for a busy 12 to 18 months, as you can see on this slide, punctuated by the completion of regulatory submissions across our core 4 programs and a tremendous amount of work by our team to prepare for launches across the board.

So with that, now, I'd like to open up for Q&A. (Operator Instructions) And if we don't get to you, we'll be able to follow up with you later. Ingrid? Operator?

(Operator Instructions) Your first question comes from the line of Cory Kasimov with JPMorgan.

I guess I wanted to ask about the sickle cell path and what it comes -- I'm just curious, what does the term "general agreement" mean at this point? Because it sounds like you have a lot of the details. But is it just in reference to waiting on further manufacturing guidance? Or are there still other aspects that need to be ironed out in terms of what might go into the filing?

And can you confirm that the Phase III 210 study is -- interim looks not going to be included, that's all just confirmatory at this point?

Yes. So I'll kick that over, Cory. Thanks for the question and the support on this. The -- just to be clear, the word "general" is certainly something that is sort of this, I'd say, more sort of categorized legal caveat, right? But at the end of the day, it doesn't change the agreements that we have -- we believe we have with the agency. And it is consistent with a path that we are pursuing that you just mentioned, and it is on the basis of 206, not on 210. So I don't think you should sort of overread the word "general" on that something. If you look back in our history, every time we comment on regulatory guidance, it's always sort of this, "We have general agreement with..." So I'd leave it at that. But Dave, do you have any additional thoughts on some of the specifics on the back end of Cory's question?

Yes. The only other nuance to what Cory asked is to address alignment on CMC as well, and we have planned engagements coming up to ensure that we're aligned on that. And we expect to have both the clinical and the CMC packages ready for the time lines that we mentioned, in '21.

Your next question comes from the line of Salveen Richter with Goldman Sachs.

Could you just comment on -- with regard to the ex U.S. rights for bb2121? How the $200 million correlates with your view of the ex U.S. opportunity here?

And just a follow-up quickly on Cory's. Can you tell us we're you stand with the Group C patients receiving commercial-grade manufactured product?

I like how you worked in 2 questions there, Salveen, as a reference back to Cory. So technically, it wasn't your question.

On the first part there, we actually are -- and Joanne can comment on more details who's been sort of at the head of that discussion with BMS. But we're actually quite comfortable that it does represent pretty significant value for us. We're quite pleased. Obviously, you do all the math and you do all the work and you project the best that you can. But we think this is recognizing the fair value of the ex U.S. sort of piece of the pie that we had. But Joanne, would you care to comment on any more details on that? Or Chip? Whichever. Maybe we'll start with Joanne.

Sure. Thanks for the question. I'm not sure I have a lot to add. I think, overall, we think the deal reflects commitment to ide-cel into the patients as well as being a sensible split of the resources. As Nick said, the value, we think we got full value there. We think in the ex U.S. territories, as you know, we always had a very passive involvement both from an operational perspective as well as a financial perspective. And so we're fully aligning the operations with the responsibilities just made sense. But overall, from a financials perspective, we're very pleased.

And thank you, Joanne. Salveen, I actually forgotten your second question related to sickle cell commercial-grade manufacturing. Can you just repeat that? I apologize.

Yes. I heard it. This is Dave. So Salveen, at the time of filing, we will have experience with both suspension lentiviral vector in the clinic as well as the adherent.

There you go. That work, Salveen?

That's great.

Your next question comes from the line of Mani Foroohar with SVB Leerink.

I guess I'll be quick with Chip. When you think about the upgrade to the adjusted operating plan, about $500 million of savings from now and mid-2020 to about mid-2022, is the right way to think of that predominantly reduced OpEx in '20, late '21, early '22? Or should we think about it as about $250 million the next 12 months, then $250 million the month after that? Just a little bit of clarity on the tempo for modeling purposes.

Mani, good question. Chip?

Yes. Thanks, Mani. Yes, I think that's -- it was important for us to achieve savings in the earlier periods. And so I think if you were to apportion that between the balance of this year, '21 and mid-'22 in a fairly uniform or linear way, I think that's a good, general way to think about it. It was important that it's not all back-end loaded.

Your next question comes from the line of Yaron Werber with Cowen.

Great. Perfect. So my question is really about 211 -- study 211, which is the high-risk stroke patients. That's now sort of been postponed indefinitely. Just give us a little bit of a sense, is that due to the cost cutting? Or is it that there's a thinking that the 210 study and maybe even 206 has some of these patients in? And if they're not, why that's an important subsegment? So just trying to understand why that's been postponed?

That's a good question. Dave will get into it, and I think you're on to it. Dave?

Yes, that's a very perceptive question. So it's actually a combination. As we gain more data from 206 and from 210, we do believe we'll be able to potentially accelerate the design, if you will, that 210 was a relatively conservative design.

On the flip side, it is also saving us funding to defer that trial. So in a way, it's a win-win in the sense that we expect to be able to redesign it when we're ready to launch that trial again.

Thank you, Yaron. Appreciate it. And if you do have 4 more questions, by all means, please give me a call or e-mail us.

Your next question comes from the line of Matthew Harrison with Morgan Stanley.

This is Kostas on for Matthew. My question is regarding the anti-BCMA, bb2121. And we saw that recently, Bristol is facing some challenges with the Juno CAR T product. So I was wondering whether there is any potential read across for bb2121.

Yes. Good question. I'll take that because I think that's best that you certainly speak to BMS on that. From our perspective, we're not anticipating any read-through, and we remain committed to the continued sort of success of 2121 and the filing that we have in. So we can't predict the future, of course. But any more specifics or concerns around that, I think it's best you speak with BMS.

Joanne, anything additional to add there? I think it's pretty straightforward, but...

No. No, I don't.

Okay.

Your next question comes from the line of Biren Amin with Jefferies.

What are the gating items on manufacturing as it relates to FDA? And I guess when would you hope to finalize the plan with FDA regarding this aspect of the filing?

You're referencing -- just to be clear, you're referencing sickle cell?

Correct.

Yes. So right now, as you heard Dave talk about in good detail is, right, the clinical alignment which is the critical piece. Then we're quite confident in now -- we've learned a lot, obviously, through the manufacturing piece of the equation with thal. So that's well underway. And then also, as we think about the -- making sure that we have all the appropriate transitions, if you will, in the various types of products that we're bringing forward with the agency. That's well underway. And that will be an ongoing discussion as it always is across all our applications. So we're not anticipating that, that's going to have an impact, and that's why we're comfortable with the time frame that we've outlined.

Dave, do you have anything additional you want to add to that?

Only to highlight, as we've said before, that there's overlap in the release testing work that we're doing to prepare for the TDT BLA. And so as Nick alluded to, we can leverage that to be ready for the sickle cell disease CMC package as well.

Yes. And the only other thing I'd add in there, I think you saw it in a press release from Hitachi that we also have established a relationship with them as it relates to forward-looking manufacturing as it relates to sickle. So we're excited to build on that partnership and continue to be able to make sure we can deliver in a commercial setting on behalf of sickle.

Our next question comes from the line of Dane Leone with Raymond James.

Congrats on the regulatory update. I just wanted to clarify maybe a couple of aspects of the redesign for the sickle cell filing. Can you just lay out what -- how that endpoint will actually be interpreted by the FDA on VOC? So are they looking for these 40-some-odd patients to have a rate of VOCs between months 12 and 24 of follow-up relative to their own respected baselines and some cut point of that would be the hurdle for regulatory approval?

And when do you need the last patient update for how much -- how long is the follow-up required before you would "lock the database" for analysis?

Thank for the question, Dane. And Dave is clearly the best to jump on that one. So Dave?

I was actually hoping you'd answer that one, Nick.

I can. I can try.

Yes, yes. So right, as you suggested in your question, we will be comparing intrapatient rates of events. So as you saw on that data slide that we presented from ASH, and you can expect a similar format as we go forward into EHA. We look at the baseline rates for each patient, and then we'll compare that to the event rates post-LentiGlobin treatment.

As I suggested, we'll be looking for a minimum of 18 months of follow-up following treatment with LentiGlobin. And really, within that, focusing on the period of 6 months after transplant out to month 18 and beyond. So we have a year or more of follow-up period post-treatment where the peri transplants, interventions like blood transfusions, et cetera, have all been washed out, and we're really seeing the true treatment effect of LentiGlobin, which by month 6 in most patients, is nearing the peak level. So we'll be looking at that follow-up interval compared to the baseline. And just as the endpoint suggests, looking for a complete elimination of severe vaso-occlusive events, which doesn't mean that every single patient in the study had to have complete elimination. There's a success criteria in which we've worked out with the agency for that.

And then in terms of the specific question on timing of patient follow-up for the completion of the data set, et cetera, we don't get into that level of granularity. But at EHA, you'll get to see an update of the status of the study.

Your next question comes from the line of Mark Breidenbach with Oppenheimer.

I guess I'm wondering if HGB-206 demonstrates a clear clinical benefit with regard to eliminating VOCs, why is HGB-210 necessary as a post-approval confirmatory study? What is 210 adding that we wouldn't be getting out of Group C?

Over to you, Dave.

Yes. Sure. So it is serving the classic role of a post-approval confirmatory trial. We are going to seek an accelerated approval on the basis of the interim data from the 206 trial. And to convert that accelerated approval to a full approval, we will provide additional follow-up and data on additional patients in 210. So it will serve the role as a confirmatory pivotal trial.

Your next question comes from the line of Vincent Chen with Bernstein.

Great. One more to follow up on the U.S. SCD filing. You mentioned that the primary endpoint was complete elimination of severe VOEs in some percentage of patients. Could you give us a little more color on how we should think about the percentage of the evaluated patients that need to meet this criteria for approval?

I will not be able to provide that additional granularity. All I can say is that you should look forward to the data we'll be presenting at EHA, and you'll have a sense of what the success rate that we're achieving so far is for this study population. And as we move forward, we'll perhaps be able to provide more granularity on our milestones for the agency in terms of success criteria, but not at this time.

Yes. And Vincent, the only thing I'd add to that is sort of if you zoom out 1 notch, right, we've been having ongoing discussions with the agency, of course, as they see the data, and we see it together evolve. And so you can also see we've been sort of shifting the endpoints as we go as we learn more. And I think what's really neat here, as Dave said in his -- and pretty powerful, as Dave said in his opening comments, is the fact that we can go to this type of an endpoint certainly displays confidence that both we and the agency have in the data and what we're seeing, right? And that's the kind of the maybe the take-home message. And then we certainly are getting to the details of your exact question. But if you zoom out a notch, this is a -- we're very excited about the fact that we can actually have this general agreement with the agency. Because it's a big deal, and I'd say it's unprecedented in that it certainly speaks to our belief in the data.

Our next question comes from the line of Matthew Luchini with BMO Capital Markets.

And congrats on the sickle cell progress. I just wanted to know, if you could, just want to get a little bit of sense given the progress you've made now with FDA, if you could provide some color on how we should be thinking about the European opportunity for sickle cell in light of what we've learned this morning from the U.S. side?

Yes. Let me just jump in at a high level here. I think at this point, well, obviously, we -- as we've done in the U.S., we continue to engage and we'll now engage with the European authorities as well and then finalize what the requirements are there. And when we have more details on that, we'll be able to share it. Europe certainly is a very important community to get to for the sickle cell population, so something we're deeply committed to.

Right now, we're happy to have a first step with the agency in the U.S. And now we're going to continue our dialogue in Europe and also make sure they have full access to all the data, and then we'll come back with the -- what we hope is a plan that we not only can get with the agency, but also can execute upon as we continue to build and launch thal in Europe. So not a lot of detail there, Matthew, but that's because we're not prepared to share that just yet as that's a sort of ongoing discussion.

Your next question comes from the line of Jason Gerberry with Bank of America.

On the beta thal Europe front, can you talk at all about the second half expectation? I presume it's mainly Germany where you'd expect your first commercial patients, those that have maybe been queued up for therapy. Just wondering if you can provide any color in terms of what's going on with the transplant sensors there? And any color just on the reimbursement process with Italian IFA Group.

Yes. And I'll ask Alison here, who runs commercial for us, to comment on that and is very engaged. I'll just say, broadly speaking, we're really excited about how the bluebirds in the various countries, in Italy and in France, in U.K. and certainly, Germany, are sort of coming through this crisis and I think are emerging in a really positive manner and have actually been able to make quite a bit of progress despite that. And this is both on the execution front, meaning in there with the qualified treatment centers and the investigators and the advocacy groups, but also with the payers and making sure we continue to advance the ball, recognizing it's all had a version of a COVID delay.

But more specifically, I'll defer over to Alison, if she'd like to comment on the question.

Yes. Thanks, Nick, and thanks for the question. You're right, our first patients, we anticipate in Germany later this year. And we have had -- we have continued to engage with physicians who are able to engage with us during COVID to understand where they are and where they are in the patient collection process. We've also been able to continue to engage with the reimbursement authorities in the markets. And I'm happy to say that those engagements continue even in Italy as that market starts to open up. So we look forward to continuing to progress our reimbursement in markets outside of Germany in addition to Germany in Europe through this year.

And Jason, the only thing I'd add to that -- thank you, Alison, is that -- and we've always said this, and certainly COVID, let's say, put an exclamation point on this, is that what '20 is about and even parts of '21 about is laying a strong foundation and really making sure, because this is a pretty sophisticated and game-changing pricing reimbursement approach that we're taking, that we're making good progress on. But again, to anchor that plus the new treatment paradigm, we're looking at this as a foundation lay, and that's the way the team is focused and driven. And so it's unlikely to be, let's say, a move the needle revenue kind of story as opposed to a solid foundation for which to build thal and then to build sickle and our subsequent products.

Would you guys be providing any updates just along the lines of just in terms of how many reservations there are at apceth, your supplier, or any other metrics around it? Just to give investors a sense of how that foundation is coming together?

At this point, we haven't provided that details. As we get closer and we get more into this, as we get going, then we'll figure out what's the most telling and sort of, it's insightful way to share the progress. That's something we're still continuing to get some visibility into. So at this point though, no, that doesn't make a lot of sense to kind of get in that detail. I'm not sure it's going to tell anyone a whole lot. But Alison, anything you'd add on that?

No. Nothing to add, Nick.

Your next question comes from the line of Michael Schmidt with Guggenheim.

I just had a follow-up on manufacturing for LentiGlobin. Could you just help us understand what your current capacity is in terms of courses per year and how do you think this might evolve until a potential launch in 2022 for sickle cell in terms of capacity, products per year, maybe with or without the suspension manufacturing process?

Yes, Michael. Good question. We haven't gotten into the details of that. What we can say is we're actually quite confident in the combination of the various forms of manufacturing, remember, not only for the vector, but also for the drug product manufacturing. That we are -- we wouldn't go out and try to commit to a regulatory time line if we didn't feel that we could deliver on the demand, right? That would be a really, really hard thing for the patient population, not to mention bluebird, if we were to do that.

So we're quite confident in the ramp and a pretty broad range in the ramp as we get going in U.S. and in Europe. And that's also partly what you see in the Hitachi relationship, right, to make sure that we have the partners out there who are pushing hard and committed to the sickle population as well. So that's not only suspension, right? Clearly, I'm making sure we can get the virus made there, but also on the drug product capability to support the infrastructure and the treatment centers in U.S. as well as in Europe.

So that doesn't give you the exact numbers you're talking about there. But quite honestly, we would not be signing up for a regulatory time line or range of time line if we didn't feel that we had the execution infrastructure behind it.

Our next question comes from the line of Alexander Duncan with Piper Sandler.

At ASCO, you will also present real-world data in late-stage myeloma patients. Could you help us understand the materiality of this real-world data update, how it compares to the KarMMa-enrolled population? And whether it is part of the BLA data package the FDA is reviewing for ide-cel?

Dave, would you like to comment?

Well, what I can offer is that it's, in a sense, an artificial control group based on attempts to match comparable populations. It should really be looked at to provide context for the KarMMa data, and I wouldn't go much beyond that.

It will be certainly insightful because, as we know, these late-stage relapsed/refractory patients have very few treatment options and their prognosis is quite poor. So I think you'll expect to see that reinforced. And again, that will help provide context for interpreting the KarMMa data at ASCO.

And also, Alex, one of the things that you can see from the top line data, and you'll be getting a further update here in just a few days, right, certainly, as you just look at the data that's been shared today, it's transformative, right? This is for the patient population that we're talking about here and the gravity of the disease that they're facing. You honestly don't need real-world evidence to say that, that is a significant change for these patients and sort of the armamentarium that the physicians have to hopefully help these patients families. So we remain super excited. And I think that's also what you see here in the BMS, for lack a better word, double down in collaboration with us on that. So we're deeply committed and believe in 2121 and its ability to have a dramatic impact on the myeloma population. Thank you, Alex.

The next question comes from the line of Gena Wang with Barclays.

I wanted to ask about the BMS royalty, $200 million. Based on our calculation, the peak sale will be much lower than $500 million. Should -- is that the benchmark? Should we think about the U.S. opportunity as well?

Not 100% sure I understand your question, Gena. You're saying you -- well, sorry, can you repeat? Unless, Joanne, you've got it and you can answer it?

Sure. Sure. So basically, based on the DCF analysis, the peak sale, based on our analysis, is roughly the $200 million translate to like maybe $500 million peak sales in ex U.S. And just wondering, would that be similar as a benchmark we should think of for the U.S. opportunity?

I don't -- I obviously don't know the details of your model. But -- and Joanne or Chip, you guys can speak to it, but I'm not sure we would agree with that math.

Yes, I think it's -- this is Chip.

Yes.

Go ahead, Chip. Why don't you and Joanne chime in?

Yes. It's a couple of things going on. There is a gross royalty, but there's also a royalty noted on behalf that we're now stepping back from. So you have to adjust for both sides of that. There are milestones as well as royalties. So it's not as simple as just looking and trying to backsolve for a revenue bid. And then again, it's not a 50-50 world. The largest opportunity within the CAR T space remains the United States. And so I think as Joanne said at the top, we feel like $200 million is fair and full value for what is still a commercial forecast with arrow bars around it because we're not there yet. But we certainly feel like fair and full value in a non-dilutive form.

Joanne, anything to add on that one?

No. No, I think that was well said.

Your next question comes from the line of Ben Burnett with Stifel.

Just a follow-up on the sickle cell discussion. And just for a little bit of clarity here, do you anticipate having pediatric patients as part of any label following accelerated approval of LentiGlobin? Or would these pediatric patients come later with the 210 study?

Yes. Great question. So the 206 trial has enrollment down to age 12, and the 210 study has a younger pediatric population included in the protocol. So as I mentioned in the introductory statements, that's one of the additional advantages of running the 210 studies that will gain experience with even younger pediatrics.

Our next question comes from the line of Josh Schimmer with Evercore.

For the U.S. sickle filing for LentiGlobin, I guess I'm a little surprised it's going to take over a year given everything we know now. Is the gating step the 18 months of follow-up for -- across the patients? And if so, does your filing time line assume that some of that follow-up can be submitted as a supplementary amendment?

Dave can speak to that. But this certainly has to do with the follow-up and the execution, but we're still actually pleased with the timing. Josh, we recognize that we look at a certain amount of data, and everyone gets excited. But you need a magnitude of the data and you need to see the longevity to the number of patients you need through that timing, right? So that adds to that bit.

Dave, anything additional you'd like to add to Josh's question?

No. I mean you're correct. So we'll want to see a minimum of 18 months of follow-up on a subset of the cohort C patients to enable the submission. And then the plan is that subsequently, we would be able to provide longer follow-up data on the 206 patients and data from 210 as well to enable confirmation of the results seen with the initial filing and conversion to full approval.

Yes. And Josh, the other way to look at this, right, as you think about some of the original plan, right, and you look at 210 and you look at that, the timing there, given also some of the complexity going on in the world right now as it relates to the pandemic and the enrollment time frames that, that brings, this really liberates us to move quite aggressively despite some of those changes given how far along we already were on 206.

So I think between the data and the strategy and the willingness and the collegiality that the agency has shown on this, it's actually a tremendous, at least from our perspective, we believe, is a tremendously positive outcome.

Your next question comes from the line of Raju Prasad with William Blair.

On the adherent for suspension manufacturing process, can you just kind of give us a sense of how that aligns with the current filings with the regulatory agencies? And as far as cost benefits, any color around how the transfer suspension would help your COGS would be great.

So I can provide a little color at the high level there, that 206 and 210 as they continue to enroll patients, we'll be doing so with the suspension product, and we have that sort of ready to go. And as patients start to get infused, et cetera, they'll be sort of live, if you will, in that sense. So that will be happening here through this period. So that's a very positive thing, obviously. And then -- so we don't anticipate, although we'll continue to refine the exact details with the agency on this, we don't anticipate that standing in the way. And certainly, from an execution point of view, internally, one of the benefits of some of the refocusings here is that we are very dedicated to make sure that we can scale the suspension capability for all our products. And that's something that's happening on internal facilities as well as external facilities at this point.

And I'll let Chip -- you can speak to the cost of goods here. But overall, obviously, they get a lot better. But that's an emphasis, that's on a go-forward basis. Now that we know, most importantly, these products really are, knock on wood, transforming the lives of patients.

But Chip, anything you would add additionally, there?

No, I think that's well said. We haven't gotten into expectation setting on our gross margins or things of that sort. But suffice it to say, suspension, it's a big boost on our front. And it gets back to some of the commentary around financial sustainability. That's a key component of it, not just to be able to deliver curative therapies, but at scale and on a business model that gets us where we want to be. So we're -- top priority for us is getting suspension over the line.

And there are no further questions at this time.

Excellent. Well, I'd like to thank everyone for taking the time this morning. And if you do have follow-up questions or anything, you can reach out to myself or to Ingrid. And I think we're good with this call.

Thank you, everybody.

This concludes today's conference. You may now disconnect.