Q1 2020 Earnings Call

[music].

Ladies and gentlemen, thank you for standing by welcome to the Bluebird Bio first quarter 2020 earnings conference call.

Emily Beynon: transcript Emily Beynon BF-WATCH TV 2021

At this time, all participants' lines or any listen only mode.

After the speakers presentation, there will be question and answer session.

A question. During this session you want me to press Star one on your telephone.

If you require any further assistance please press star zero I.

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

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Bluebird Bio first quarter 2020 earnings conference call. At this time, all participants' lines are in a listen-only mode.

Thank you and good morning, everyone.

Ingrid Goldberg Investor Relations at Bluebird bio.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. If you require any further assistance, please press star zero.

And welcome to today's conference call to discuss our quarterly earnings and the business update.

I'm joined today by several members Bluebird management team.

Well not today's call will be opening remarks from Nick.

Sickle cell disease regulatory update from days.

Complete the call with highlights my revised operating plan from Chip. We will then turn to your question.

Before I begin I would like to remind everyone that our discussion today includes forward looking statements under the private Securities Litigation Reform Act 1995.

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

Such forward looking statements are based on our current expectations and assumptions that are subject to risks and uncertainties actual results may differ materially from those expressed today due to a variety of factors.

Additional information concerning these risk factors that are filings with the FCC and available on the Investor section of our website at Www Dot Bluebird bio dot com.

As a reminder, well we may elect update forward looking statements in the future does not undertake any obligation to update forward looking statements, even if our expectations changed except as required by law.

You should not rely on these forward looking statements as representing our expectations at any big subsequent to today.

With that I'll now turn the call Liberty.

Thank you and grid.

Ingrid Goldberg: 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.

Ingrid Goldberg: Before I begin, I would like to remind everyone that our discussion today includes four 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 is in our filings with the SEC and available on the investor 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.

We've always done we start by reminding us all why we do what we do.

Nick: Thank you, Ingrid. As we've always done, we start by reminding us all why we do what we do. The Y. 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 why.

Our industry faces very tough blogs and it is easy to lose the narrative well get discouraged by the never ending battled to find medicines that matter.

Belief is that the odds are best overcome by deeply caring and making a personal.

The walls don't seamless tall order sick, whereas painful to run into if we focus and people are focused on the why.

The Koeppen 19 pandemic has reminded us all how fragile life can be and also how important it has to come together in times of need.

Nick: 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 frontlines, as well as perhaps serve to re-establish some of the lost public and political trust of our. 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 the safety of our employees but also to work tirelessly with our 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 are just amazing.

Personally proud of how are industry responded to the crisis and hopefully soon we'll be able to deliver medicines to the front lines.

As well as perhaps served to reestablish somebody that loss public and political trust over industry.

Specific to Bluebird I'm extremely pleased to witness how the team has responded to the crisis to knowledge scramble to ensure a business continuity and safety of employees, but also the work tirelessly with our clinical sites manufacturing partners and everyone necessary to ensure we do right buyer patients and their families.

Inside and outside the company, we've seen folks stepping up and all sorts of ways with truly inspirational and very schuman leadership, the positivity passion and focus on the silver linings, It's just amazing.

The impact to the pandemic on Bluebird is not yet fully know and we intend to remain vigilant as we continue to navigate the best we can until normal operations resume.

Nick: 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 show the tremendous progress in not only developing a revised operating plan but also in advancing our key development program. 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 a major milestone. Let me cover several recent critical miles.

With that as context I'm all the more excited to show the tremendous progress and not only developing a revised operating plan, but also in advancing our key development programs.

[noise] the progress has been significant across many fronts further solidifying the fundamentals are bluebirds vision for patients and our operational strength to execute.

First we recently hit.

First let me cover several recent critical milestones.

With our partners up BMS, we shared exciting topline results for Karma study back in December.

Nick: With our partners at BMS, we shared exciting top-line results from a CARMA study back in December, and in Q1 of this year, we submitted the U.S. BLA for EIDA cell for the treatment of late stage multiple myelitis. 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 lentiloban and sickle cell disease, with plans to file for approval in the second half of 2021.

And in Q1 of this year.

Submitted the U.S.P.L.A. either sell for the treatment of late stage multiple myeloma.

Stay tuned for an updated data presentation at this year's virtual ask a meeting and for a data summary pressing release press release this coming on Wednesday may 13th once you ask on Barco 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 lend people open 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 year chain meeting in mid June.

Nick: 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 Zintaglo commercial ramp-up in Europe, US approval and launch of EIDA cell, and the US filings of lentid for CLD, lentidlobin in thalassemia, and now lentidlobin in sickle. 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 IDACEL and monetized our XUS rights for $200 million to add to our operational resources and flexibility.

Overall 2021 is on track to deliver several major milestones, including synthetic looks and take little commercial ramp in Europe, U.S. approval and launch of Ida So and the U.S. filing so plenty de for C.L.D., let people open in the fallacy EMEA and now let people open in sickle cell.

Second as promised on our March 26 update call. We've made significant progress on the operational front to reflect the changes to our plans and the unknowns brought on by the Cobot 19 pandemic.

Notably we've optimized our relationship with BMS to best serve either so and monetize directionless 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 operating plan through mid Twentys 22.

Nick: 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 four 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 short-sighted objectives that can kill innovation and organizational drive to success. I'm very happy to report that this is not the case at Blue.

Finally, as chip will share in more detail.

The revised plan extends our runway into 2022, while keeping our core for late stage programs and pipeline promise intact.

The operating budgets 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 the budget cuts and program changes can tear apart accompanies 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're 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.

Nick: We are keeping our eyes on the horizon and what will give 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 it is not over yet, we strongly believe we will not only come through this time healthy but actually be 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 to 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.

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, reaching 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.

Our fundamentals are even more sound as weve 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 updates and as a refresher as we approach he ha in June.

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. Basal 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 HGV-206 group C, each bar represents a patient in the study who had at least six months of follow-up. On the left is the pre-treatment 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.

I'd like to remind you of the high point of the clinical data looks like he gogo for sickle cell disease now we presented it asked last year.

Basically inclusive crises represent the quintessential clinical manifestation of sickle cell disease.

He's painful and life threatening crises may completely derail the lives of patients with sickle cell disease, often leading to hospitalisation progressive reversible organ damage and increased morbidity and mortality.

Price needs as well as stroke.

Most clinically meaningful endpoints for patients and clinicians.

On this data figure from at capturing the frequency of evasive occlusive crises and acute chest syndrome and patients from study HCV to US six group see each bar represents a patients in the study who had at least six months fall out.

On the left.

As the pre treatment time period with each all to frequent red diamond representing an event.

The right side of the figure shows the follow up period after Atlantic woven infusion and remarkably we see a 99% reduction in crises.

These data truly communicate the transformative potential lengthy wasn't gene therapy.

Dave: 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 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.

The impressive magnitude of the treatment effect has recently enabled a positive and productive type b meeting with the FDA 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 to US six study results at USA.

Next slide.

Our prior development plan to support approval consisted of the phase one to two of six study and the phase three HCV to 10 study.

Dave: Our prior development plan to support approval consisted of the Phase 1-2-206 study and the Phase 3-HgV-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. This approach was intended to support accelerated approval based on observing favorable interim results for globin response in HGV-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.

Our initial goal what's your six was to establish the correlation between hemoglobin based outcomes captured as the globin response primary endpoint.

And the occurrence evasive occlusive event.

Which was the key secondary endpoint.

This approach was intended to support accelerated approval based on observing favorable interim results for globin response in HCV to 10.

On the basis of the 26 data our recent discussion with the FDA has provided alignment on a new path to of the L.A., which is shown on this slide.

In agreement with the FDA, we have updated the primary endpoint. The joystick study to be complete resolution of severe faisal inclusive of that 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 groups see the touristic study.

Dave: With this change, we are planning to seek accelerated approval based on a subset of patients in Group C of the 206 study. The global response endpoint will shift to being the key secondary. 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.

The globe in response endpoint will shift to being a key secondary endpoint.

Well, we are not specifying a 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 and accelerated approval. The initial data submitted on complete resolution of severe Vega Offences events will serve as an intermediate clinical endpoint to be subsequently confirmed with longer fall.

Given the clinical data package, we have outlined we anticipate being able to submit our U.S.P.L.A. in the second half of 2021.

Dave: Given the clinical data package we have outlined, we anticipate being able to submit our USBLA in the second half of 2021. In parallel, we will continue to move forward with the Phase III H2B210 study, which will serve as a post-approval confirmatory study. This study will allow us to evaluate pediatric patients with sickle cell disease.

In parallel we will continue to move forward with the phase three HSV 210 study, which will serve as a post approval confirmatory study.

This study will allow us to evaluate pediatric patients in sickle cell disease.

In addition to treating patients in the E U and gaining additional experience with suspension lentiviral vector.

Dave: In addition to treating patients in the EU and gaining additional experience with suspension lentiviral vector, these two 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.

These two studies together well build a comprehensive clinical dataset 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.

Dave: As Nick mentioned, we have made meaningful progress not only in sickle cell disease but across our late stage clinical program. We, in partnership with Bristol-Myers Squibb, recently submitted the US BLA for Idacel 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 Karma Study as part of this year's virtual ASCIM. Our CRB402 Phase 1-2 study of BB21217 in patients with relapsed refractory multiple myeloma remains active, but enrollment has slowed due to COVID-19, which for our patients with TDT has highlighted the risk of being tethered to frequent blood transfusions.

We in partnership with Bristol Myers Squibb recently submitted the U.S.P.L.A. for Ida sell 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're also looking forward to presenting data from the pivotal Karma study as part of this year's virtual Alaska meeting.

Our CRB forero two phase one two study of BB 21, 21, seven in patients with relapsed refractory multiple myeloma remains active but enrollment has slowed due to covert 19.

Despite the global challenges from covert 19, which for our patients with T. T has highlighted the risk of being tethered to frequent blood transfusions. We've been pleased with the progress made by our blue birds and external partners present, peglow in Europe in consenting and preparing patients for treatment in Germany.

Dave: We are pleased with the progress made by our bluebirds and external partners for Zenteglo 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 HEV 207 and 212 pivotal studies. And finally, we are pleased that Lempi-D for CALD remains on track for planned regulatory filings in the EU this year and in the US next year, and we anticipate providing updated clinical data for LentE-D at a medical meeting later this year. And with that, I'll turn the call over to Chip.

As well as forgetting access and reimbursement and additional EU countries.

We look forward to providing updates it yesterday for our ongoing HCV to a seven and to 12 pivotal studies.

And finally, we are pleased Atlanta de for C.L.D. remains on track for planned regulatory filings in the E. U. This year and then the U.S. next year, and we anticipate providing updated clinical data for Latin 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 outline our revised operating plan, an updated financial guidance on todays call.

Chip: Thanks, Dave. Good morning, everyone.

Chip: I'm pleased to outline our revised operating plan and updated financial guidance on today's call. The last two months have been a time of unprecedented change with the COVID pandemic and the profound impact on the economic and capital markets outlook. Despite these dramatic changes to the macro environment, the fundamentals of our business remain strong. 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 continue 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 four 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 secure non-dilutive funding and extend financial services online. As you heard at the top from Nick, we were successful in all of these goals.

The last two months had been at time of Unprecedent change with the cobot pandemic and the profound impact to the economic capital markets outlook. Despite these dramatic changes to the macro environment the fundamentals of our business remains strong.

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 continue to prove out the transformative patient impact about products, we're seeking to balance our commitment to cutting edge innovation with the plan that moves forward towards financial and operational sustainability.

Our goals and this plan or fourfold number one deliver the core floor to patients in the commercial setting by 2022.

Second I continue to innovate by advancing most promising components in the pipeline and platform technologies.

Third.

Scale and grow the business at a more balanced and sustainable rate.

And for.

Secure non dilutive funding and extend financial runway.

As you heard at the top from Nick we were successful against all these goals.

Moving onto slide nine we can go deeper on the revised I'd have thought collaboration with BMS.

Chip: Moving on to slide nine, we can go deeper on the revised IDSL collaboration with CMS. 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, under the terms of the revised collaboration, over time, bluebird will transition vector manufacturing to responsibilities to BMS for the ex US manufacturing, while bluebird will continue to manufacture vector to support the US market. And BMS is paying Bluebird $200 million in exchange for our future rights to milestones and royalties related to EIDA cell and db 2121 seven outside the United States. We're very pleased with the revised collaboration for a number of reasons. First, we have operational alignment in the U.S. and ex-U.S. geographies.

This was more than simply a financial transaction and there are a broader set of strategic takeaways that are good program good for patients and good for BMS and Bluebird.

To recap terms about the revised collaboration.

Overtime Bluebird will transition dr. manufacturing to responsibilities to BMS for the actually that's manufacturing.

Bluebird will continue to manufacture vector to support the U.S. market.

And BNS is paying bluebird $200 million, an exchange to our future rights to milestones and royalties related to I'd itself and D. V 21, 21, seven outside the United States.

We're very pleased with the revised cooperation for a number reasons.

First we have operational alignment in the U. S and X U.S. geographies.

We have secured 200 million a non dilutive funding.

For the company had a critical critical time.

Chip: We've secured $200 million in non-diluted funding for the company at a critical time. And, most importantly, we have shared commitment with DMS to EIDA cell, and both sides are investing aggressively to deliver for patients. As you heard from Nick, we are excited to share the full karma data set at the upcoming ASCO conference later this week.

Most importantly, we have shared commitment would be enough to either sell and both sides are investing aggressively to the looking for patients.

As you heard from Nick we're excited to share the full comedy to set at the upcoming ASCO Conference later this month.

Moving on to Slide 10, Oh highlight a the details of our revised operating plan.

Chip: Moving on to slide 10, I'll highlight the details of a revised operating plan. On the left 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 four core programs.

Hi on the left hand side of the page you see the non Negotiables in terms of what how did movies resource and funded in our plan.

It starts with the core for programs and here, we're seeking regulatory approval and commercial launch of the U.S. in Europe by 2022.

Chip: And here we're seeking regulatory approval and commercial launch in the US and Europe by 2022. Moving on to the core four doesn't happen without manufacturing, and here we're seeking to secure the supply chain for our pending commercial launch and making the transition to suspension by de-biovector manufacturing. This is critical from both the cost of goods perspective and the capacity perspective. Research is a critical part of the revised operating plan, and we are prioritizing support for the core four, expansion of core four potential through technologies like reduced toxicity conditioning, car preserved apheresis, and suspension LVV, promising preclinical programs that could be in the clinic in the next one to two years. And last but certainly not least, two of our most important assets: people and culture.

Moving onto the call for doesn't happen without manufacturing and here we are seeking.

To secure the supply chain for pending commercial launch and making the transition to suspension Lentiviral vector manufacturing. This is critical for both the cost of goods.

Effective and a capacity perspective.

[noise] research is a critical part of the revised operating plan and we're prioritizing support of the court for.

Expansion of core for potential future technologies like reduce toxicity conditioning, cryopreserved decreases and suspension LTV.

And.

The promising preclinical programs that could be in the clinic and the next one two years.

And last but certainly not least two of our most important assets people and culture. This plan supports continued investment there and keeping blue bird flu and all the way it's that people come to know.

Chip: This plant supports continued investment there and keeps Bluebird blue in all the ways that people have come to know. On the right side of the page, you can see where we were able to prioritize and drive savings versus the prior plan. This includes facilities taking actions to reduce our facility footprint and fix 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 HDB 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, preclinical program. With this revised operating plan, we 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 where we are today. Happy to answer any questions in the Q&A.

On the right inside 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 SGN, a build out which is more in line with the commercial timing of forecast.

Label, expanding studies I don't know, most notably HCB, two and one 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 our completion.

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, we're committed to our long term financial sustainability.

Nick: But for now, we'll turn it back to Nick.

Balancing the innovated side of our business the Gotta swimwear today.

Happy to answer any questions in the United but for now I'll turn it back to Nick.

Thanks Chip, it's a lot to digest, what we feel it's exciting an important progress towards launching or first four programs optimizing our business, where the path forward and doing so without cutting bonus we say that won't grow back preserving what we call R&D with a sole.

Nick: Thanks, Chip. It's a lot to digest, but we feel it's exciting and important progress towards launching our first four programs, optimizing our business for the path forward, and doing so without cutting any bones, 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 four programs and a tremendous amount of work by our team to prepare for launches across the. So with that now, I'd like to open up for Q&A. We're going to try to get to as many people as possible, but we do ask that you limit yourself And if we don't get to you, we'll be able to follow up. Ingrid, operator.

It 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 all our core for 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 acuity, we're going to get to try to we're going to try to get to as many people. It's possible, but we do ask you limit yourself to one question and if you don't get you will be able to follow up with you later.

In grid operator.

At this time I'd like to remind everyone. If you looked like you asked a question. Please press Star then the number one on your telephone keypad.

Operator: At this time, I would like to remind everyone, if you would like to ask a question, please press star and then the number one on your telephone keypad. Your first question comes from the line of Corrie Kamoff with J.P. Morgan.

Your first question comes from the line of core he came off of JP Morgan.

Hey, good morning, guys. Thanks for taking the question for all the color today, I guess I wanted to ask I'm about to sickle cell path and it what it comes I'm just curious what does the term general agreement mean at this point 'cause it sounds like you have a lot of the details but is it just in reference to waiting on further manufacturing guidance or.

Corrie Kamoff: Hey, good morning, guys. Thanks for taking the question for all the color today.

Nick: I guess I wanted to ask about the sickle cell path and what it comes down to. 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 for 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 3 to 10 study is the interim looks not going to be included? That's all just confirmatory at this point. Thanks a lot.

Are there still other aspects that need to be ironed out in terms of of what might go into the filing and can you confirm that the phase three to tighten study is <unk> didn't interim looks not gonna be include. This is that's all just confirmatory at this point thanks a lot.

Yes, I'll kick that over Corey Thanks for the question and the support on this the just to be clear. The word general is certainly something that is this a I'd say more.

Nick: Yes, so I'll kick that over. Corey, thanks for the question and the support on this.

That's sort of categorized legal caveat might go but at the end of the day. It doesn't change the agreements that we have a we believe we have with the agency and it it is consistent with a path that we are pursuing.

And that you just mentioned and it is on the basis of two six not on to 10.

So I don't think you should sort of over read the were generally that's something if you look back in our history. Every time, we comment on regulatory guidance. It's always a sort of this we have general agreement with so I I'd leave it at that but Dave do you have any additional thoughts on some specifics on the back end of course question.

Dave: 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, or 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. That's something if you look back on our history, every time we have commented 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 Corey's question?

I yeah, the only other nuanced what a core he asked us to address a alignment on C.M.C. as well and we have planned engagements are coming up to ensure that were aligned on that and we expect to have both the clinical in the CMP see packages are rare.

Dave: Yeah, the only other nuance to what Corey 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 CMPC packages ready for the timelines that we mentioned, 21.

The for the timelines that we mentioned 21.

Okay. Thanks, guys.

Thank you Corey.

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

Dave: Okay, thanks guys. Thank you, Corey.

Salveen Jaswal Richter: Your next question comes from the line of Salveen Richter with Golden. Good morning. Thanks for taking my question. Could I just comment on the ex-U.S. rights for BB 2121, you know, how the 200 million correlates with your view of the ex-U.S. opportunity here? And just to follow up quickly on Cory's question, can you tell us where you stand with the group C patients receiving commercial grade manufactured products?

Good morning, Thanks for taking my question and I, just comment with regard to the X U.S. rights for each when he went to anyone you know how the 200 million correlates with Youre beginning with the ex U.S. opportunity here and just a follow up quickly on core east and can you tell us where you stand.

With that group C patients receiving commercial grade manufactured product.

Thanks.

I like how you worked in two questions are suffering as a reference back to Corey So technically it wasn't your question.

Nick: I like how you worked in two questions there, Salveen, as a reference back to Corey, 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, so 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 XUS 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 you, Anne. Sure.

[laughter] on the on the first part there we actually are and join can comment on on more details who's been sort of at the head of that discussion with with BMS, we're actually quite comfortable that it does represent pretty significant value for us. We're quite pleased obviously you could do all the mass and you do all the work and you projected best that you can.

But we think this is a recognizing the fair value of the ex us sort of piece of the pie that we had but Joanne would you care to comment on any more details on that or or chip whichever.

They will start shortly.

Sure. Thanks, Thanks for the question I'm not sure I have a tad I think overall, we think the that you will reflect a commitment titus onto the patients as well.

Joanne: Sure. Thanks for the question. I'm not sure I have a lot to add. I think overall, we think the deal reflects, you know, commitment to IDSL and to the patients, as well as being a sensible split of the You know, as Nick said, the value, we think we got full value there. We think, you know, 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 response. But overall, from a financial perspective.

The resources, you know as Nick said.

The value, we think we got full value there.

We think you know any extra territories as you know, we always had a very passive involvement.

Problem I from an operational perspective, as well the financial perspective, and so we're probably aligning the operations with the responsibilities.

But overall from a financial its perspective, we're very pleased.

Joanne: But overall, from a financial perspective, we're very And thank you, Joanne, Salveen, I actually have forgotten your second.

And thank you Joanne Salvia and I actually.

Forgotten your second question related to sickle cell commercial grade manufacturing can you just repeat that I apologize yeah I heard it. This is Dave so Saudi and at the time of filing we will have experienced with both suspension lentiviral vector in the clinic as well as the adherent.

Joanne: Yeah, I heard

Dave: This is Dave. So Salveen,

There you go.

And that weren't troubling.

That's great. Thank great. Thank you for the questions.

Dave: There you go.

Dave: That works, Salveen.

Your next question comes from the line of many from Horwitz, It's <unk>.

Dave: That's great. Thanks.

Dave: Great, thank you for the questions.

Mani Foroohar: Your next question comes from the line of Mani Foroohar with SVB. Hey guys, thanks for taking my question. I guess I'll be quick with Chip. When you think about the adjusted operating plan, about $500 million of savings from now in mid-2020 to about mid-2022, is that the right way to think of that predominantly reduced OPEX in late-21 and early-22, or should we think of it as about $250 million the next 12 months, $250 million the month after that? Just a little bit of clarity on the tempo.

[music].

Hey, guys. Thanks for taking my question I guess with RB quickly chip when you seemed to be up into the adjusted operating plan about slumps 500 million August savings from now in mid 2022 about mid 2022 is the right way to think of that predominantly reduce opex in 20 late.

21, early 22 or should we think about it is about about 250. Your next 12 month 250 million the month after that just a little clarity on that on the tempo for modeling purposes.

Manny Good question chip.

Yeah. Thanks, Ronny I, Yeah, I think that's.

Chip: Mani, a good question. Chip?

It was important for us to achieve.

Chip: Yeah, thanks, Mani. Yeah, I think that 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 that's a good general way to think about it. It was important that it wasn't all back end voted.

Savings in the earlier periods and so I think if you are to the portion that between the balance of this year 21, and mid 22, and then in a fairly.

Uniform or linear way I think that that's a good general way to think about it. It was important that's not all backend loaded.

Great. That's helpful. I will not still a second question [laughter]. Okay. Thank you really have a great day.

Chip: Great, that's helpful. I will do it now.

Chip: [inaudible]

Your next question comes on line of your Ron Werber with Cowen.

Chip: Okay, thank you. Have a great day! Your next question comes from the line of Yaron Werber with Cal. Great. Thanks for taking my five questions.

Great. Thanks for taking my five questions [laughter] go for your own hang up on after the first.

Perfect.

So my question is really about to 11 study to 11, which is the high risk stroke patients. That's now sort of been postponed indefinitely and just give us a little bit of the sun is that due to the cost cutting or is it but there's a thinking that the 210 study and maybe even to six.

Yaron Werber: You're playing up on you after the first Perfect. So my question is really about 2.11, study 2.11, which is the high-risk stroke patients that have now sort of been postponed indefinitely. Just give us a little bit of a sense, is that due to cost cutting, or is it that there's a thought that the 2.10 study and maybe even 2.06 have some of these patients in, and if they're not, you know, why? That's an important sub-segment, so just trying to understand why that's been postponed. Thank you.

Some of these patients in and if they're not you know why that's an important sub segments is trying to understand why that's been suppose thank you.

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

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

Yeah, that's a very perceptive question, so it's actually a combination.

Dave: Yeah, 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.

As we gain more data from two Essex and and from 210.

We do believe well be able to potentially accelerate the.

Design, if you will Ah that's a you know to 10 was a relatively conservative design I'm on the on the flip side. It that it is also saving us Oh funding to defer that trial. So in a way. It's it's a a win win in the sense that we expect to be able.

The redesign that when we're ready to a a launch that trial again.

Thank you I appreciate it.

And I do have four more questions by all means please just give me a color email us.

Dave: Thank you, Ron. I appreciate it. And now, if you do have four more questions, by all means.

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

I'm and went beyond [noise].

Matthew Harrison: Your next question comes from the line of Matthew Harrison with Morgan. Hello everyone, this is Costas on behalf of Matthew. Thank you for taking my question. My question is regarding the anti-BCMA BB2121, and we saw that Bristol is facing some challenges with a Juno CAR T product, so I was wondering whether there is any potential read across for BB2121. Thank you.

This is a close that's on for Mark you. Thanks for taking my my question.

My question is Ed Garding be on they'd be see it may be btwenty, one trend UAN and we saw about the recently, but he's still is facing some talent d., we the Juno crappy product. So I was wondering whether that is any potentially read that cross for B B 21 21. Thank you.

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 21, 21, and and the filing that we have in.

Nick: Yeah, good question. I'll take that because I think it'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 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.

So we can't predict the future of course, but any more specifics or concerns around that I think as best you speak with BMS joint anything additional to add there I think it's pretty straightforward but.

No no no okay.

Thank you like you're welcome.

Nick: No, no I don't. Okay.

Nick: OK.

Your next question comes from the line of Marine I mean with Jefferies.

Yeah, Hi, guys. Thanks for taking my questions one of the gating items on manufacturing isn't really that FDA and I guess when would you hope to finalize you know the plan with the FDA regarding the this aspect of the filing.

Unnamed Questioner: Your next question comes from the line of... Yeah, hi, guys. Thanks for taking my questions. Um, 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?

Nick: the plan with FDA regarding this aspect of the filing. You're referencing sickle cell, just to be clear, you're referencing sickle cell?

Oh, you're referencing just to be clear you're referencing.

Sickle cell.

Correct.

Yes, so right now we as you heard Dave talk about in a good detail is right the clinical alignment, which is the critical piece and then we're quite confident and now we're we've learned a lot obviously through the manufacturing pieces equation with south so that's a well underway and then also as we think about the making sure that we have older. The appropriate transitions. If you will in the various types of products that we're bringing.

Nick: Correct.

Nick: Yeah, so right now, as you heard Dave talk about in good detail, is right, the clinical alignment, which is the critical piece, and then we're quite confident in now, we've learned a lot, obviously, through the manufacturing piece of the equation with Sal, so that's well underway, and then also, as we think about 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'll be an ongoing discussion, as it always is across all our applications, so we're not anticipating that that's going to have an timeframe that we've outlined. Dave, do you have anything additional you want to add to that?

Forward with the agency, that's well under way and that's the that'll be an ongoing discussion as always is across all their applications. So we're not anticipating that that's gonna have an impact and that's why we're comfortable with the timeframe that we've outlined Dave do you have anything additional you want to add to that.

Hi, 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 T T. The L.A. and and so as Nick alluded to on we can leverage that to be ready for the sickle cell disease CMC package as well.

Dave: 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.

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

Dave: Yeah, and the only other thing I'd add is that, I think you saw it in a press release from Hitachi, 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.

Awesome. Thank you.

Okay.

Your next question comes from the line of Dang, the young with Raymond James.

Unnamed Questioner: Awesome. Thank you. Your next question comes from the line of Dane Leone with Raymond J. I thank you for taking our questions and congratulations on the regulatory update. I just wanted to clarify maybe a couple aspects of the redesign.

Hi, Thank you for taking my questions.

Congrats on the regulatory update I just wanted to clarify maybe a couple aspects of the redesign a for the sickle cell filing.

Can you just.

Dane Vincent Leone: design for the sickle cell filing. Can you just lay out how that endpoint will actually be interpreted by the FDA on BSD? So are they looking for these 40

Layout, what how the endpoint will actually be interpreted by the FDA.

On.

DSD. So are they looking for these 40, some odd patience to have a rate of video sees between months 12 to 24, a follow up relative to their own respect the baselines and some point of that would be the hurdle for regulatory approval and what when do you need the last pay.

Update or how much how long does the follow up acquired.

Operator: [inaudible]

Before you would quote unquote lock the database for analysis.

Thanks for the question here and Dave's clearly, though the best to jump on that one so Dave.

Operator: , , , , ,

I was actually helping you to answer that one Nick I'm glad I [laughter] I can try yeah. So.

Right as you as you suggested in your question, we will become pairing.

Intra patient a 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 and each day.

We look at the baseline rates for each patient and then a will compare that to the event rates post Atlantic Little been hot treatment as I suggested we'll be looking for a minimum of 18 months of follow up I'm. Following our team Atlantic well then.

And really within that focusing on the period of six months after transplant out two months 18 and beyond so we have a year or more a follow up period post treatment, where the Perry transplants.

Operator: And we have a patient update for how much how long is the follow up required before you would quote unquote lock the database.

On a interventions like blood transfusions et cetera have all been washed out and we're really seeing a the true treatment effect of I'll, let you go up and which by month sex and most patients is nearing the peak level I'm. So we'll be looking at that follow up interval compared to the baseline and add just as the endpoints.

Dave: The database for analysis.

Suggest looking for a complete elimination of severe vasopressin events, which doesn't mean that every single patient in the study has to have complete elimination. There's a success criteria in which we have worked out with the agency for that and then in terms of a specific question on timing of patient follow.

A lot for on the completion of the dataset et cetera, we don't get into that level of <unk> granularity, but.

At the end shale, you'll get to see a an update of the status of the study.

Excellent. Thank you very much like you could question appreciate it.

Dave: Thanks for the question here, and Dave's clearly the best person to jump on that one. So, Dave.

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

Hey, good morning, guys and thanks for taking the question I'm just I'm wondering if each QB two six demonstrate the clear clinical benefit with regard to eliminating views sees why is each TB to 10 necessary as a post approval confirmatory study what is to 10, adding that we wouldn't be getting out of a group C.

Thanks for taking my question.

Over you Dave Yeah sure. So yeah. It is serving as a classic roll out of a post approval confirmatory trial.

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

We are going to seek and accelerated approval on the basis of the interim data from the two most six trial and a two kind of hurt that accelerated approval to a full approval, we will provide additional follow up and.

Dave: I could try.

Data on additional patients into 10, so it will serve the role as a confirmatory our pivotal trial.

Thank you Mark.

Your next question comes on the line of instant Chan with Bernstein.

Great. Thank you very much for taking the question a little more volatile in the U.S.C.D. filing you mentioned the primary endpoint was complete elimination of severe view, even some percentage of vision.

One more color and how we should think about the percentage of evaluations and need to meet this criteria for approval.

I will not be able to provide that additional granularity I'm. All I can say is that a you should look forward to the data will be presenting it he ha and you'll have a sense of what the success rates that we're achieving so far is for this study.

Population.

And as a as we move forward will perhaps to be able to provide more I'm granularity on our milestones for the agency in terms of success criteria, but not at this time.

Vincent the only thing I'd add to that is sort of if you assume out one notch right. We've we've been having ongoing discussions with the agency of course as they see the data and we see it together involved and so you can obviously, we've been sort of shifting the endpoints as we go as we learn more and I think what's really need here as Dave said in his and pretty powerful as Dave said in his opening.

Dave: 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

Comments is the fact that we can go to this type of an endpoint or certainly displays confidence both we and the agency having the data on what we're seeing right. That's that's and that's the kind of that maybe the take home message and then we certainly are they getting to the details of your exact question, but if you assume 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 a big deal and I'd say, it's unprecedented and certainly speaks to our belief in the data.

Thank you very much.

Welcome.

Your next question comes in a lot of Matthew.

Yeah, I'm old capital markets.

Hi, Good morning, Thanks for taking my question on congrats on the telephone progress I just want to know if you could just wanted to get a little bit effect given the progress you've made now with Ftn. If you could provide some color on how should be thinking about the European opportunity.

Dave: 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 peritransplant interventions like blood transfusions, etc., 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 end point suggests, looking for There's a success criterion which we've worked out with the agency for that. And then, in terms of the specific question and timing of patient follow-up for the completion of the data set, etc., we don't get into that level of granularity, but at EHA, you'll get to see an update on the status of the study.

For sickle cell in light of what we've learned a this morning from the U.S. side, Yeah. Let me just jump in a at a high level here I think at this point, where obviously, we as we've done in the U.S., we continue to engage and will now engage with the European authorities as well and then finalized what the requirements are there as well we have more details on that we'll be able to share it you're up certainly as.

Very important.

Community to get to for the sickle cell population. So it's something we're deeply committed to right now and 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 Oh, 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 a south in Europe, so not a lot of detail there Matthew but that's because we're not prepared to show that just yet is that so sort of an ongoing discussion.

Fair enough. Thank you.

Thank you good question it's important.

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

Dave: Excellent

Hello, Good morning, Thanks for taking my questions.

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 are those that are maybe been cued up for therapy. Just wondering if you can provide any color in terms of what's going on with with the transplant centers, there and any color just don't need to reimbursement process.

Dave: Thank you very much.

Italian ice.

Great. Thank you.

Yeah, and Alaska Allison here runs commercial for us to comment on that and it's very engaged I'll just say broadly speaking, we're really excited about how are the bluebirds in the various countries in Italy, and France in UK, and certainly, Germany or or sort of coming through this crisis and I think are emerging in a really positive manner and I've actually been ever make quite a bit of price.

Mark Breidenbach: Thank you. Good question. I appreciate it.

Gross despite a that and this is a both on the execution front, meaning in there with the classified treatment centers and investigators and they have she groups, but also with the the payers and making sure. We continue to advance the ball recognizing it's all had a version of a have a covert delay, but more specifically I'll defer over to Alison.

She'd like to comment on the question.

Yeah, I think snacking and thanks to the question.

You're right.

Eight in Germany later, this year and Oh, we have.

Hi.

Gauge, what physicians, who are able to engage with us during cold it to understand where they are and where they are on the TV collection process. We've also.

Been able to continue to engage with.

Reimbursement authorities in the markets and I'm happy to say that doesn't gauge that continue even in Italy as a that market starts to open up. So we look forward to continuing to progress progressed, our reimbursement in markets outside of Germany. In addition to Germany in.

Europe through this year.

Jason One thing I'd add to that thank you Allison is that and we've all we've always said this in certainly cobot or let's say put an exclamation point on this is that what what 20 is about and even parts of 20 wants to buy the 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 land. That's the way the team is focused in 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 the build Sal and then to build cycle and or subsequent products.

It would you can see providing any updates along the lines just in terms of how many reservations there are asked Kevin.

Our 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 we get closer and we get more into this as we get going then we'll figure out what's the most telling him sorta its 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 us make a lot of sense to kind of get in that each I'm not sure it's going to tell anyone a whole lot.

What else anything you'd add on that.

No nothing that okay. Thank you.

Thank you Denise you.

Your next question comes on line of Michael Schmidt with Guggenheim.

Hey, guys. Thanks for taking my questions I just had a follow up on manufacturing for Atlantic You know Ben could you just help us understand what's your current capacity is you know in terms of courses per year and how do you think this might evolve until you know potentially launching 2022.

Dave: Your next question comes from Mark Breidenbach with... Hey, good morning, guys, and thanks for taking the question. 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? Thanks for taking the question.

Dave: Over to you, Dave.

Let's take up sell in terms of capacity now products per year, or you know maybe with or without these expansion manufacturing process.

Yeah, Michael Good question, we haven't gotten into the details of that what we can say is we're actually quite confident 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 timeline. If we didn't feel that we could deliver on the demand right that would be.

Dave: Yeah, 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. And it will serve the role of a confirmatory pivotal trial.

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 in a pretty broad range and the ramp as we get going and U.S. and in Europe, and that's also partly what you're seeing that tachy relationship might to make sure that we have the partners out there, who pushing hard and committed to the sickle population as.

So that's not only suspension right clearly on making sure we can get the virus made there, but also on the drug product capability to support the infrastructure in the treatment centers in and U.S. as well as in Europe. So it doesn't give you the exact numbers you're talking about there.

But quite honestly, we would not be signing up for regulatory timeline or range of timeline. If we didnt feel that we had the execution infrastructure behind it.

Okay. Thank you.

Thank you Michael.

Your next question comes on line of Alexander Duncan with Piper Sandler.

Dave: Thank you, Mark.

Vincent Chin: Your next question comes from Vincent Chin with... Great, thank you very much for taking the question. One more question on the U.S. SED 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?

Hi, Good morning, Thanks for taking my question at after you all to present real world data in late stage myeloma patients could you help us understand the mute materiality of this real world data update how it compares to the Karma enrolled population and whether it is part of the BRL eight.

Dave: 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 success criteria, but not at this time.

Data package. The FDA is reviewing for either so thank you.

Dave would you like to comment.

Oh, well what I can offer is that it's in a sense say.

An artificial control group based on attempts to match or comparable populations. It should really be looked at add to provide context for the karma data.

And Ah you know I I wouldn't go much much beyond that it will be certainly insightful because as we as we know these late stage relapse refractory patients that very few treatment options and their their prognosis is quite poor so I think.

We'll expect to see that I reinforced and and again that that will help provide context for interpreting me the karma data at ASCO.

And also Alix one of the things that you can see from the topline data and you'll be getting a further update here in just a few days right certainly should just looking to date has been shirt. Today is it's transformed my this is for the patient population, we're talking about here and the gravity of the disease that they're facing you know you honestly don't need real world evidence to say that that is a significant.

Nick: Yeah, and

Changed fruit for this patients and that sort of the armamentarium that the physicians have dolefully help these patients and their family. So we remain Super excited and I think that's also what you see here in the BMS blank better words double down in collaboration with us on that so we're deeply committed and believe in 21 21 and a its ability to really have a dramatic impact on the myeloma.

Population.

Next question I'm from the line of Gena Wang with Barclays.

Thank you for taking my question.

Oh, yes, well you teach <unk> Nissan Oh wishing you the people well will be much lower than <unk>.

She.

Well bore benchmark should we think about the U.S.P. as well.

No, 100% sure I understand or your question Geno, you, you're saying you.

Sorry can you repeat unless Joanne you got it and you can answer okay.

So.

No you sounded yeah I know you know the peak you know.

Relative to lead the 200 million translate into like maybe 500 human T cell.

Right.

I'm, just wondering how would that be similar.

Well I'm tomorrow, we should think though with the U.S. optimism.

I don't I'm, Bobby you don't know the details your model, but a and Joanne or chip you guys can speak to it but I'm not sure we would agree with that math.

Yeah, Yeah chip.

Going to just wondering to jump in.

Yeah, I, it's <unk> a couple of things going on.

The there isn't a grocer, okay, but there's also royalty ordered on behalf.

Yeah, we're now stepping back from so you have to.

I just for both sides of that there are milestones as well as royalties. So it's not as simple. It's just what you're trying to back salt for a revenue did and then again, it's it's not a.

50, 50 world that they need largest opportunity within the car T space remains the United States and so I think this giant said at the at the top you know we feel like 200 is a powerful value for you know what is still a.

Correct Unforecasted error bars around it they're not there yet, but we certainly feel like a trickle down and in an anomaly that would have one.

Joining anything to add on that one.

No no I think that was also great. Thank you.

Thank you Jim.

Your next question comes on the line up in Burnett with Stifel.

Hi, Thank you good morning.

Just a follow up on the sickle cell discussion.

Just a little bit of clarity here do you anticipate having pediatric patients as part of any label. Following accelerated approval. Once you go up and or would these pediatric patients come later with with the 210 study. Thank you.

Yeah, Great question, so that that to a six trial has enrollment down to age 12.

Nick: And, Vincent, the only thing I'd add to that is sort of if you zoom out one 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 all see that 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 opening comments, and pretty powerful, as Dave said in his opening comments, is the fact that we can go to this type of endpoint certainly displays the confidence that both we and the agency have in the data and what we're seeing, right? And that's kind of 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, 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, and it certainly speaks to our belief in the data.

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 a the 210 studies that will gain experience with even younger PDR.

Correct.

Thank you Dave.

Your next question comes on line of Josh Schimmer with Evercore.

Matthew: Thank you very much. You're welcome. Hi, good morning. Thanks for taking the question and congrats on the sickle cell progress. I just wanted 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 learned this morning from the U.S. side.

Hey, Thanks for taking the question for the U.S. sickle filing for went to go up and I guess Im a little surprised it's going to take over a year given everything we know now is getting a step the 18 month follow up for across the patient Philip So does your filing timeline, assuming that some of that follow up can be submitted as.

Nick: Let me just jump in at a high level here. I think at this point, obviously, as we've done in the U.S., we continue to engage and will now engage with the European authorities as well, and then finalize what the requirements are there. When we have more details on that, we'll be able to share them. Europe certainly is a very important community to get to know for the sickle cell population, so it's something we're deeply committed to. Right now, we're happy to have taken 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 what we hope is a plan that we can agree with the agency but also can execute upon as we continue to build and launch SAL 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 sort of an ongoing discussion.

Matthew: Fair enough. Thank you.

Jason Gerberry: Thank you. Good question. It's important.

As a supplement turned the amendment.

Dave can speak to that but it certainly has to do with the follow up in the execution, but we're still actually quite pleased with the timing Josh we recognize that you know 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 do that bit, but I'm, Dave anything additional you'd like that it's Josh is question.

No I mean, your if you're correct, so well well or want to see a minimum of 18 months a follow up on a subset of the cohort C patients to enable the submission and then a the plan is that subsequently we wouldn't be able to provide.

Longer follow up data on a that to a six patients and data from 210 as well.

To enable a confirmation of the results seen a with.

The initial filing and conversion to full approval.

Yes, 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 that the timing there given also some of the complexity going on in the world right now as it relates to the pandemic and enrollment time frames that that brings this really liberate system move quite aggressively despite some of those changes given how far along we already.

We're on tool six so I think between the data on the strategy and the willingness on the collegiality that the agencies shown on this it's actually a a tremendous at least from our perspective, we believe it's a tremendously positive outcome.

Thank you.

Okay.

Your next question comes from the line that's right you probably saw with William Blair.

Allison: Your next question comes from the line of Jason Gerberry with Bank of America. Hello, good morning.

Thanks for taking my question.

On the adherence for suspension manufacturing process can you just kinda give us a sense of how that aligns with the current filings with regulatory agencies and as far as cost benefits any color around you know how they transfer suspension would help your cogs would be great. Thanks.

Allison: Thanks for taking my questions. On the beta cell, you're up 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 the Italian IFA group. Thank you.

Nick: Yeah, and I'll ask Allison here, who runs commercial for us, to comment on that, and she is very engaged. But I'll just say, broadly speaking, we're really excited about how the bluebirds in the various countries in Italy and in France and the UK and certainly Germany are sort of coming through this crisis and, I think, are emerging in a really positive manner.

Allison: And I've 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 investigators and the advocacy groups, but also with the payers and making sure we continue to advance the ball, recognizing that they all had a version of a COVID delay. But more specifically, I'll defer to Allison if she'd like to comment on the question.

So I can provide a little color at the high level there that tool six to 10 as they continue to enroll patients will be doing so with the suspension product and we have that sort of ready to go in and as patients start to get infused et cetera, there'll be a sort of live if you will in that sense. So that'll that'll be happening here through this period. So that's a very positive thing.

Allison: Yeah, thanks, Nick. And thanks for the question. You're right.

Allison: Our first patients are anticipated in Germany later this year, and 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 selection 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 will continue even in Italy as that market starts to open up. So we look forward to continuing to progress reimbursement in markets outside of Germany in addition to Germany in Europe this year.

Allison: And Jason, the only thing I'd add to that, thank you, Allison, is that, and we've always said this, and certainly COVID, let's say, put an explanation point on this, is that what 20 is about, and even parts of 21, are 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 But again, to anchor that plus the new treatment paradigm, we're looking at this as a foundation, 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 build Sickle and our subsequent products.

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

Allison: At this point, we haven't provided that detail, but 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 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 into that detail. I'm not sure it's going to tell anyone a whole lot. But Allison, anything you'd add to that?

Eric Thomas Schmidt: No, nothing yet. Thank you. Your next question comes from the line of Michael Schmidt with Guggenheim. Hey, guys, thanks for taking my questions. I just had a follow-up on manufacturing lentiglobin. Could you just help us understand what your current capacity is, you know, in terms of courses per year? And how do you think this might evolve until, you know, the potential launch in 2022 for sickle cell in terms of capacity, you know, products per year, you know, maybe with or without the suspension manufacturing process?

Nick: Yeah, Michael, good question. We haven't gotten into the details of that yet.

Nick: 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 timeline 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 of the ramp as we get going in the US 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 cell population as well

Nick: So, that's not only suspension, right, clearly on 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 the US as well as in Europe. So, that doesn't give you the exact numbers you're talking about, but quite honestly, we would not be signing up for a regulatory timeline or range of timelines if we didn't feel that we had the execution infrastructure behind us.

Obviously and then so we don't anticipate all the will 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 refocusing Sears that we're very dedicated to make sure that we can scale the suspension capability for all our products and that's something that's happening on a internal facilities.

That's was external facilities at this point and I'll, let chip you can speak to the cost of goods here, but overall, obviously, they're getting a lot better but that's a an emphasis on a go forward basis now that we know a most importantly, these products really are knock on wood transforming the lives of patients, but chip anything you'd add additionally, there.

No I think that's all said, we haven't gotten into expectations study in on our gross margins are things that sort, but.

Suffice to say just mentioned is a big boost on that front.

It gets back to my 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.

This model what got you get this only want these were.

Top priority for us it's a good just mentioned over the one.

Thanks.

Welcome.

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 that you can reach out to myself or to Ingrid.

Nick: Okay, thank you.

Alexander Duncan: Thank you, Michael.

Dave: Your next question comes from the line of Alexander Duncan with Piper Sandler. Hi, good morning, and thanks for taking our question. At ASCO, you will also

Dave: In late-stage myeloma patients, could you help us understand the music?

Dave: is reviewing for IDISO. Thank you. Dave, would you like to comment?

And I think we're good with this call thank everybody.

Dave: 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 CARMA 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 CARMA data at ASCO.

Nick: Yeah, 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 arsenal that physicians have to hopefully help these patients and their families. So we remain super excited, and I think that's also what you see here in the BMS, for lack of better words, double down in collaboration with us on that. So we're deeply committed to 2121 and its ability to really have a dramatic impact on the myeloma population. The next question comes from Gina Wang with Barclays.

Huidong Wang: Thank you for taking my question. So I wanted to ask about the DMS volatility, 200 million. Based on our calculation, the peak sale will be much lower than 500 million. Is that the benchmark? Should we think about the US opportunity as well?

This concludes today's conference you may now disconnect.

[music].

Nick: I'm not 100% sure I understand your question, Gina, but you're saying you

Nick: Well, sorry, can you repeat that unless Joanne you you've got it, and you can answer it.

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

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

[music].

Chip: Yeah.

Chip: I don't pretend to be a kid.

Chip: Yeah, there are a couple things going on. There is a gross royalty, but there's also a royalty owed to it 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. It's just worth trying to back solve 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, um so I think, as Joanne said at the top, you know we feel like 200 is uh... terrible value for uh... what is still a uh... commercial forecast with error bars around it uh... because we're not there yet but we certainly feel like uh... terrible value uh... and in a non-dilutive form.

Chip: Do I have anything to add?

Chip: No, no. I think that was well said.

Huidong Wang: Thank you, Gina.

Unnamed Questioner: Your next question comes from the line-up in Burnett with Stiefel.

Dave: Hey, thank you. Good morning. Just to follow up on the

Operator: [inaudible]

Operator: And just for a little bit of clarity here,

Dave: Thank you.

Josh Schimmer: Yeah, 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, which will gain experience with even younger pediatrics.

Dave: Thank you, Dave.

Dave: Your next question comes from the line of Josh Schimmer with Evercore. Hey, thanks for taking the question.

Josh Schimmer: 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 across the patients? And if so, does your filing timeline assume that some of that follow-up can be submitted as a supplement or an amendment?

Dave: Dave can speak to that, but this certainly has to do with the follow-up and the execution, but we're still actually quite pleased with the timing. Josh, we recognize that, you know, 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 of the number of patients you need through that timing, right? So that adds to that bit. But, Dave, anything else additionally you'd like to add to Josh's question?

[music].

Dave: Um... Um... Um...

Dave: 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.

Nick: Yeah, and Josh, the other way to look at this, right? 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 enrollment timeframes that that brings, this really liberates us to move quite aggressively, despite some of those changes, given how far along we already were on 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 outcome, at least from our perspective. We believe it's a tremendously positive outcome.

Nick: Your next question comes from the line of Raju Prasad with William Blair. Thanks for taking the question on the

Raju Prasad: adherence versus suspension manufacturing process. Can you just kind of give us a sense of

Nick: of how that aligns with the current filings with the regulatory agencies, and as far as cost benefits.

Nick: Any color around you know how the transfer suspension would help your cog?

Chip: That would be great. Thanks.

Chip: be great. Thanks.

[music].

Nick: So I can provide a little color at the high level there that 206 and 210, as they continue to enroll patients, will 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. And that's it.

Nick: So that'll 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 refocusing here is that we are very dedicated to making sure that we can scale the suspension capability for all our products. And that's something that's happening in the 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'd add additionally there?

Chip: No, I think that's well said. We haven't gotten into expectation setting on gross margins or things of that sort. But suffice to say, suspension is a big boost on that front, and it gets back to some 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 our top priority for us is getting suspension over the line.

Chip: Thanks. You're welcome. And there are no further questions at this time.

Operator: Excellent. Well, I'd like to thank everyone for taking the time this morning, and if you do have follow-up questions or anything, then 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.

Operator: [inaudible] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , music music music music music music music music music music music music music music music music music music music music E E E E E E E E E E E E E E E E, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , music music music music music music music music music music music music music music music music music music music music music music music music music music music music music music music music music music