Liz Pingpank – Associate Director, Corporate Communications Nick Leschly – Chief Executive Officer Mohammed Asmal – Vice President, Clinical Development Philip Gregory – Chief Scientific Officer.

Salveen Richter – Goldman Sachs Schimmer – Evercore ISI Eric Schmidt – Cowen & Company Cory Kasimov – JP Morgan Jim Birchenough – Wells Fargo Matthew Harrison – Morgan Stanley Dane Leone – BTIG Michael Schmidt – Leerink Partners David Nierengarten – Wedbush Securities Matthew Luchini – BMO Capital Ying Huang – Bank of America Vincent Chen – Bernstein Biren Amin – Jefferies Huidong Wang – Barclays.

Good day, ladies and gentlemen, and welcome to the bluebird quarterly update and ASH 2017 Abstract Call. [Operator Instructions] I’d now like to introduce your host for today’s conference, Ms. Liz Pingpank. Ma’am, you may begin..

Nick will make some opening remarks, and then will walk through the clinical abstract will share a preclinical update and Nick will then conclude and we’ll open up the call for Q&A. Before we begin, let me review our safe harbor statement.

Today’s discussion contains statements that are forward-looking under the Private Securities Litigation Reform Act of 1995. Such statements are based on current expectations and assumptions that are subject to risks and uncertainties and involve a number of risk factors that could cause actual results to differ materially from projected results.

In particular, statements, whether the changes to the SGB clinical trial protocol, including mobilization will improve outcomes in patients for severe sickle cell disease and risks that the current or planned clinical trials of LentiGlobin in thalassemia will be sufficient as per regulatory submission or marketing approval in the U.S. and EU.

Additional information concerning these risk factors contained in our filings with SEC, which are available on the Investor Relations section of our website, www.bluebirdbio.com.

While we may elect to update forward-looking statements in the future, we specifically disclaim any obligation to do so even as 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. I’ll now turn it over to, Nick..

Thank you, Liz, and thank you, everyone, for joining us on the call this morning. Our objective today is to highlight our quarterly progress and share the emerging data included in some of our ASH abstracts. In the past, we’ve generally not done a quarterly call or a webcast for abstract releases.

But in case, we felt it was important to provide the context for the new data. In particular, we’ll focus on some limited data on our 206 study in sickle cell disease as well as updates on our 2014 thalassemia study. Our goal is cover 2 simple questions.

What is the relevance of the new data? And what are the expectations now going into ASH? Before we dive into the data, we always start off by talking about why we’re here? And simply put, it’s about hope. It’s about doing all that we can to bring hope to patients and the families is desperate need in. True Blue captures that idea for our patients.

And BLUE MOJO captures everything we do inside the company to make that dream come true. So how do we succeed? While you’re hopefully will notice about team blue is that we believe success lies in our ability to continuously innovate and learn about both our gene therapy platform as well as the underlying disease biology.

We spent much of 2017 talking about key learnings in both these areas. On the technology front, we’ve been seeking to improve on our product as well as manufacturing to optimize all aspects of our programs. Specifically, we shared our new manufacturing process for LentiGlobin.

The PI3-kinase manufacturing edition of BCMA, and inn this call will share our research into the plerixafor – into using plerixafor for sickle cell disease mobilization. On the biology front, we’ve been focused on going deep in our understanding of the pathophysiology of disease and using that to inform innovations in our approach.

We further our understanding of patients genotypes in thalassemia, implement a protocol changes in sickle cell disease to addressing challenges, and more recently, share deep cell phenotyping in both and sickle cell.

The point is simple, by innovative and integrating our learnings in both technology and biology, we believe we’ll continually deliver the absolute best for patients. Today, we announced our quarterly financials and recent operation progress. As we progress through the year, we’re achieving many other goals we set at the beginning of the year.

Notably, this quarter, we disclosed significant progress in our BCMA program related to the treatment of the first patient of the expansion cohort of Phase I CRB-401 trial, a bb2121 as well as treatment of the first patient in the Phase I trial of our second-generation candidate bb21217.

We also disclosed our interim data in early October from our Phase II/III trial in showing that 15 out of 17 of the patients had met the primary endpoint.

Just last week, we also received the regenerative medicine advanced therapy designation also known as for our sickle cell program for the FDA – from the FDA, enabling early and formal engagement on our development plans. Lastly, we continue to be well funded with $1.1 billion of cash on the balance sheet, taking our runway into 2020.

Our focus moving forward is clear and an exciting evolution of the company. We’re preparing the company for future product filings and commercial launches, and building towards our 224 and 2020 vision. 2-plus commercial projects, 2-plus nearing commercial and 4-plus pipeline products. It’s very exciting times.

Now let’s shift gears and focus on the ASH data. I’m happy to say that this is going to be the biggest bluebird – this is going to be bluebird’s biggest ASH ever. And with 11 presentations across our clinical and preclinical programs. Most of the abstracts are placeholders with no data.

However, several of the abstracts made public today contain some new and important data. On the front, there is an updated to the HGB-204 study, also known as Northstar. On the sickle cell disease front, there is an update on the HGB-206 study, including data on the safety of using plerixafor as a mobilizing agent in patients with sickle cell disease.

But for clarity, today, we will not be providing updates on either of the BCMA program or the studies, also known as Northstar-2. But new data on both will be provided at ASH in a few weeks.

We also have several preclinical contracts – abstracts, one of which will be in touch – we will touch on briefly today related to our relationship with Boston Children’s Hospital and their preclinical program in sickle cell disease. Before I turn the call over to Mohammed for the data review, let me give you the quick highlights.

On sickle cell disease. The question is whether any of our improvements in protocol changes are going to make a difference for sickle cell disease patients? The good news is that the early clinical data is a promising step forward, including our ability to shift towards space product using plerixafor mobilization.

On our clinical and regulatory path remains on track based on the updated 204 data. With that free preview, I will hand it over to Mohammed to review the data.

Mohammed?.

Thank you very much, Nick. Let me start with a quick overview of our 4 studies of LentiGlobin and thalassemia. HGB-204, also known as Northstar and HGB-205, our Phase I/II study conducted in patients of all genotypes using the original manufacturing process. These 2 studies will form the primary basis of our filing in the European Union.

The ASH abstracts provide an update on the 204 study that I will present today. HGB-207, known as Northstar-2, is our Phase III study in patients with non-beta-0/beta-0 genotypes while transfusion dependent.

The 207 study is conducted using the improved manufacturing process, which substantially increases both the drug product copy number and the proportion of stem cells by the vector. The 207 study is ongoing. And as Nick mentioned, the ASH abstract does not include any new data. So we will not update this study today.

HGB-212, known as Northstar-3, is our Phase III study in patients with thalassemia who have the beta-0 genotype. These patients make no 212 is also conducted using the improved manufacturing process. We are on track to start 212 this year, and will announce when the first patient has been treated with LentiGlobin.

Now that you’re oriented, I’ll walk through an overview of the Northstar Study. As mentioned today, abstracts include an update to the Northstar Study. 18 patients have been treated in this study. 10 patients with non-beta-0/beta-0 genotypes and 8 patients with the beta-0/beta-0 genotypes. And they have a median follow-up of 26 months.

Of the 10 patients with the non-beta-0/beta-0 genotypes, 8 have been free from transfusions for median of 27.1 months. At the last study visit, these 8 patients had a total hemoglobin ranging from 9.3 to 13.7 grams per deciliter with T87Q hemoglobin ranging from 3.6 to 9.6 grams per deciliter.

The other 2 patients with non-beta-0/beta-0 genotypes have seen the annual transfusion volumes reduced by 30% in 1 patient and 94% in the other. Notably, these 2 patients received drug product at the low end of the range in the study, 0.3 and 0.4, respectively.

There is a strong correlation between DP VCN and T87Q hemoglobin production in the thalassemia studies. So the outcomes in these 2 patients with low drug product is not a surprise, but rather the importance of introducing the improved manufacturing process to optimize transduction efficiency.

In the patients with the beta-0/beta-0 genotype 2 of the 8 have not received a transfusion in more than a year. At the last study visit, for these 2 patients, total hemoglobin levels were 9.0 and 10.2 grams per deciliter, with T87Q globin levels of 8.2 and 6.8 grams per deciliter.

These patients have vector copy numbers in the higher range of what we saw with the original manufacturing process. With subsequently robust of 0.9 and 0.6, respectively. The remaining 6 subjects with beta-0 genotypes have seen their annual transfusion volume decreased by median of 63%. Across these patients, we have not seen any new safety signals.

And the safety profile to date has been typical for conditioning. These results show clinically meaningful benefit in the great majority of the patients. With 8 of the non-beta-0/beta-0 and 2 of the beta-0/beta-0 patients, now free of transfusions for at least a year and transfusion reductions in the remainder.

Importantly, these data reinforce the potential clinical benefit from the improved manufacturing process implemented in our Northstar-2 and Northstar-3 studies.

Using this process, we expect to achieve more consistently robust T87Q production to mitigate against patient-to-patient variability and enable an even a higher proportion of patients to become free of transfusions with near normal or normal total immunoglobulin levels.

Looking forward, the Northstar-2 study will be key to our demonstrating the clinical impact of the manufacturing improvements for patients with TDT.

At this year, we presented early data from our Northstar-2 study, which showed that with the improved manufacturing process, we are able to consistently produce drug product with a higher and percentage of cells The improvement in drug product into higher levels of T87Q globin in the clinic, and at EHA, we showed That Patient 1 was producing 9.5 grams per deciliter T87Q at 6 months of follow-up, enough to be free of transfusion based on T87Q alone.

At ASH, we will provide updated data on the 3 patients we presented at EHA as well as new data on approximately 5 additional treated patients.

With the growing body of clinical data on LentiGlobin in thalassemia, we’re making preparation for the filing and launch of LentiGlobin for patients with thalassemia, first in the European Union and then in The United States.

As we described our Gene Therapy Day event in 2016, we have general agreement from the regulatory authorities in The United States and European Union on the path forward.

In the EU, we’re working through the framework of the prime designation and adaptive pathways to file for conditional approval in patients with non- beta-0/ beta-0 genotypes on the basis of the NorthStar and the 205 studies, and including available interim data from 207.

In The United States, we have breakthrough therapy designation and plan to file for a full approval in patients with non-beta-0/beta-0 genotypes based on data from the Northstar-2 study. We plan to provide more clarity on timelines in 2018. Lets now switch gears to discuss sickle cell disease.

We’re fortunate that first patient we treated, Patient 1204 in Paris, who is the subject of a case study published in the New England Journal of Medicine earlier this year had a successful treatment this month and provided important lessons for optimizing outcomes in sickle cell disease.

By improving how we patients through stem cell collection and transplant as well as driving improvements in our drug product manufacturer. In the first cohort of patients treated in our HGB-206 study, we saw a large drop from drug product vector number of peripheral vector number shown on this slide.

And the low was associated with low levels of T87Q globin. Consequently, achieving improvements in both drug product has been a major focus for us over the past year.

We have implemented several changes to study protocols intended to address this drop in which we see largely as a problem of The changes include low transfusions intended to reduce inflammation and hypoxia of the bone marrow to improve both the quality of stem cells and improve of the drug product.

More stringent conditioning to effectively eradicate competition from residual uncorrected cells; changes to the manufacturing process to increase cell dose; implementation of improved process as we did in our thalassemia programs to increase drug product vector copy number and percentage of cells Finally, evaluating the feasibility of using plerixafor mobilization and rather than bone marrow harvest to improve the number and quality of stem cells collected from patients.

I will start out with the description of the different stages of the 206 protocol to clarify how the changes have been implemented sequentially.

Group A, the original version of the HGB-206 protocol using the original manufacturing process, where none of the variables outlined had been In contrast, in HGB-205, the single study in France, all patients had received preharvest transfusions and conditioning.

And the differences in outcomes between 205 and group A helps to inform the protocol changes we implemented in 206. Group B. We have optimized across almost all of the variables, but stem cell collection is still viable harvest. Today, we will have a first look at data showing the impact of these changes in 2 patients. Group C.

This group consists of patients whose stem cells have been collected by mobilization and and today we will share the safety data an initial drug product characteristics using this approach.

To set the stage for the 206 results, included in today’s abstract, next I will show you data from the 205 study that we presented at which highlights the positive impact of red blood cell transfusions and stringent myeloablation on both in vivo and T87Q production. The red lines represent the 206 patients in group A.

And the blue dotted lines represent the 205 patients. In the figure on the left, the Y- axis shows on a large scale because of the wide range of values across the patients. And the Y axis in the figure on the right shows the amount of T87Q globin.

Patient 1204 represents an optimal outcome, but early data from the subsequent 2 patients treated in Paris indicate they are also on a positive trajectory.

These patients who are optimized across some of the variables we have discussed, including preharvest transfusion and stringent myeloablative conditioning, but their stem cells are collected by bone marrow harvest, and they did not receive drug product manufacturing with the improvements now incorporated into 206.

It is encouraging to see that the baseline transfusions and stringent myeloablation in 205 improved in vivo and T87Q relative to 206 and we hope to see an even greater favorable impact with the additional protocol changes now in place for the 206 study. The 206 ASH abstract includes new early data from 2 patients treated in group B.

The first treated patient, 1313, was treated with a mix of 2 drug product lots. One manufactured using the original process and one with the improved process, providing of 1.4 and 3.3, respectively. The second patient 1312 was treated with 2 drug product lots manufactured using that new process. And these lots have vector copy numbers 5.0 and 2.9.

In the figures, you can see the dramatic improvement in and the percentage of transduced cells achieved with optimizing manufacturing shown in green Compared to the original manufacturing process shown in red. The early data in the group B patient is shown in green on the next figures.

And it shows how the manufacturing and protocol changes have achieved our goal of substantially improving in vivo and T87Q globin production.

The first patient treated in group B 1313 has a peripheral of of 0.5 at the last visit, month 3, which is higher than all of the patients in group A and also above the patients in HGB-205 with the exception of patient Level 4.

At 3 months post-infusion, patient 1313 is producing 1.5 grams per deciliter of T87Q, which is higher than the results for any prior 206 patient at that time point. The second patient, 1312, was treated with 2 lots manufactured using the refined manufacturing process. At one month, shortly after the patient has a peripheral VCN of 2.6.

This in vivo VCN exceeds all other patients in the 206 trial treated to date. At the time of the abstract submission, the initial T87Q value was not yet available for this patient.

These early results provide evidence that the modifications to the study protocol have improved drug product and in vivo VCN and we anticipate these improvements will translate into increased production of T87Q globin. We will provide further follow-up data at ASH on the in vivo VCN and levels of T87 Q production in these 2 patients.

The final modification of the study protocol is the implementation of plerixafor mobilization and to collect stem cells rather than bone marrow harvest. Mobilization and is expected to yield both improved numbers and improved quality of stem cells.

But had not previously been used for patients with sickle cell disease because of historical data that GCSF, the glycoprotein typically used for mobilization can trigger severe crisis by virtue of inducing significant leukocytosis in activation of leukocyte and endothelial cells.

We and others have been investigating whether with single agent plerixafor might be used safely since it induces a less intensive leukocytosis and does not activate cells does. Importantly, will substantially improve the patient experience as it represents a less invasive procedures in bone marrow harvest.

This abstract presents data on 3 patients with sickle cell disease, who hafe undergone plerixafor mobilization and We are encouraged that the mobilization in procedures have had an acceptable safety profile with no dose-limiting toxicity is observed.

In these 3 patients, we have collected cell doses of 15.3, 5.6 and 9.0 million CD34 cells per kilogram. This is approximately double the average cell collection of 5 million CD34 cells per kilogram achieved with bone marrow harvest. And no subsequent or mobilization was required to achieve these cells.

Pace early results suggest we can safely collect substantially higher cell doses using plerixafor mobilization and apheresis.

In addition to patient convenience and increased cell dose, our analysis of cells collected using plerixafor mobilization and apheresis suggest that these cells may have a significantly larger proportion of stem cells compared to those collected by bone marrow harvest.

These true primitive stem cells have high expression of CD34, and mainly and repopulation of the the bone marrow following transplantation. Analysis of the cells obtained through bone marrow harvest shows that on average 41% of them are called CD34 themselves.

The cells are low expressers of CD34, and therefore, probably do not represent the true stem cells that are required for and the population of the bone marrow to with cells that will ultimately differentiate into the and express T87Q globin.

By comparison, on average, only 8% of the cells collected through plerixafor mobilization and apheresis are suggesting that a far larger proportion of these cells are true stem cells. This analysis is preliminary, and we expect to present additional data at ASH to further characterize these cell populations.

Based on the favorable data we have seen on safety and improved cell dose and the early indication that cells with a more phenotype, we are implementing the next stage in the 206 protocol to proceed with transplant using LentiGlobin drug product derived from plerixafor-mobilized cells.

Additionally, due to the promising initial experience with plerixafor mobilization, we and our study investigators decided to include only 2 patients in group B and place all subsequent patients in group C.

Further detail on the drug products manufactured for these groups C patients will be provided at ASH., however, the post transplant in vivo clinical data for these patients will not be available until 2018.

To recap, the updated data in thalassemia from 204 study indicates that a high proportion of patients with thalassemia of non-beta-0 genotypes become free of transfusions and that the benefit is durable.

Even two patients with the beta-0 genotype achieved transfusion independence, and the mean transfusion reduction was substantial with the original manufacturing process.

This trial results reinforce the importance of optimizing efficiency to achieve robust reduction of T87Q globin and underscore the importance of the refined manufacturing process that has been implemented in the pivotal trials.

At ASH, we will provide an update on a 207 in which patients have been treated with drug product with substantially improved VCN. In sickle cell disease, the early data from our group B patients suggest that the changes to the study protocol and manufacturing process have even in cells collected by bone marrow.

At ASH, we will provide additional follow-up data to show how the improved in vivo VCN translates to T87Q production. We were encouraged to see that the initial clinical cohort of patients treated in 206 have had a reduction in clinical events compared to baseline. But this observation requires a larger sample size and longer follow-up to confirm.

Our initial clinical experience with plerixafor mobilization and apheresis suggests it is well tolerated and improves both the number and quality of stem cells that are collected. We will present additional data characterizing these cells at ASH, and the impact of different cell populations may have on clinical outcome.

To date, the safety profile of LentiGlobin is comparable to transplantation in cell condition. Now Philip will discuss the preclinical abstract..

Thanks, Mohammed. The clinical programs we have several preclinical at ASH highlighting work done by our academic collaborators as well as our team of scientific and development bluebirds in Cambridge and Seattle.

These abstract shared some light into our preclinical work in immunotherapy and and we look forward to sharing further detail at ASH and hopefully in the future as some of these programs progress. One preclinical abstract worth highlighting comes from a study conducted by Dr.

David Williams and his team at Boston Children’s Hospital, representing a novel and very promising approach to address sickle cell disease by of fetal hemoglobin. And importantly, simultaneously the pathological hemoglobin S. This approach uses our lentiviral vector core technology to deliver a targeted adapted RNA, which I is quite a mouthful.

Put more simply, this vector results impression of exclusively in cells. Reduced levels are associated with of fetal hemoglobin or which is is known to the signs and symptoms of sickle cell disease.

The preclinical data generated by the bluebird team and Boston Children’s Hospital showed that of from sickle cell disease patients with this novel lentiviral vector followed by the of these modified HSE into blood cells resulted in dramatically increased expression of the hemoglobin F, ranging from 70% to 80% of all change.

Moreover, this increase in HPF is with suppression of disease-causing hemoglobin S to levels of just 19% to 30%. These results compare favorably to preclinical data on HPF presented to date with gene editing technologies, which have shown approximately 40% HPF under similar experimental conditions.

Our may represent a powerful novel therapeutic approach to sickle cell disease, which stands upon all the advances we have made with respect to a sickle cell biology, manufacturing advances and patient management, which Mohammed walked you through earlier. We’re pleased to be collaborating with Dr.

Williams and his team, and look forward to providing details of exciding preclinical data ASH. We anticipate this program will advance into the clinic in 2018. And we plan to shed more information as the program progresses. And with that, summary of the preclinical abstracts at ASH, I’ll hand the call back over to Nick..

Thank you, Philip. As I mentioned in my opening remarks, this has been an incredibly busy and productive quarterback. And ASH will certainly continue that trend with 11 accepted abstracts and clinical updates across all of our ongoing – nearly all of our ongoing clinical trials.

Just to make sure we’re clear to what we will disclose at ASH, here is an overview.

Additional follow-up on 204 as well as 205, which will form the basis – the primary basis of the EU filing from LentiGlobin An update on Northstar-2 or 207 study that will include a few more patients that have been treated with the improved manufacturing process and longer follow-up on the patients we showed at EHA.

Further updates on the 206 sickle cell disease study will include longer follow-up on the two patients we just shared in group B. We will have some product, some drug product data for several additional subjects in groups C, who had their cells collected using plerixafor mobilization.

We will also have an update on a BCMA program that will included follow-up on the 21 patients presented at ASCO. Lastly, we’ll hope you will join us on Sunday, December 10, at ASH, where he will host a webcast investor and analyst event to provide more detail and context on our clinical and organizational progress.

That companies of formal part of our content. And I look forward to take some questions.

Operator?.

[Operator Instructions] Our first question comes from Salveen Richter from Goldman Sachs. Your line is now open..

Thanks for taking my questions.

So just with regard to the sickle cell program, could you just remind us what the age or tell us what the age of these two patients are? And given your at 1.5 to 3 months, what’s the threshold level you’re trying to achieve here for this patient? And remind us what Patient 1204, the first patient treated ever showed at this time point?.

Okay, so thank you Salveen I appreciate the questions. So first maybe Mohammed, you can address the age, and then we’ll step through the other questions..

Yes, so our age range in the studies 18 and older are two subjects followed in that range. Older than traditional patients treated with sickle cell disease. Then in regards to the HPA T87Q production, so the results that are in the abstract represent the highest T87Q production at that time point of any patient does report, including 1204.

So not substantially greater than 1204, but greater than 1204. So I missed a lot..

What’s the third question, Salveen..

when we put the 1.5 in context, how should we think about this threshold T87Q level you’re trying to achieve long-term here for this to be meaningful?.

Yes. No, I think that’s an excellent question. So I think part of the answer to that question is we have to see how the data play out and how our clinical results evolve over time.

The short answer is that in subject 1204, we had approximately 4 to 5 grams of T87Q production, and that resulted essentially a conversion of that patient to biochemical trade. I think will be a very admirable goal to go forward.

I think based on historical data, with hemoglobin F production, we know that individuals that have approximately 30% of the total have significant attenuation of their symptom. So I would say that shooting for similar goal for our T87Q, which behave similarly to hemoglobin F would be something we are trying for..

And Salveen, it’s a little too early obviously. This has a very nice trajectory as you can see in the data. But we’ll provide a little more context as we go.

But I don’t think we all need to get up to the 1204 level, but our point was to really and the primary emphasis here is have we address some of the challenges, so we can get more visibility into connecting to with with sort of drug product copy number with in-vivo copy number and how that translate into beta 87.

It really wasn’t easy for us unless we can address the challenge. And this is certainly of that..

Right. And just one follow-up if I can and this might be too early as well.

But do you have any update on what endpoints the FDA may focused on here with sickle cell?.

Yes, you’re right. You asked question on that Salveen. little too early. We certainly are looking at this data, and as the data continues to evolve with a keen eye on what’s the appropriate sort of level of information, if you will, but we’re – we got a first more critical mass and consistency. And that we’ll engage with agency.

But right now, the one thing we do know is that the regulatory agency has been quite engaged with us, providing most recent of the designation. So those will be pretty significant engagement. They certainly are aware and very concerned around the plight of sickle cell disease in this country and globally.

So we feel, at least if we show up with good data, we’ll be able to engage in a very active and constructive dialogue about what the appropriate threshold is for a registration study..

Thank you..

Thank you, Salveen..

And our next question comes from from Evercore ISI. Your line is now open..

Thanks for taking my question.

Can you talk about factors that will cause a difference between the vector copy number in the cells infused versus what’s measured in the peripheral blood? Clearly, the percent engraftment will be important determination, but what are the other factors that might cause those numbers to be different?.

A little trouble, at least I’m hearing you. Can you just restate the question there? Josh, I am sorry..

Sorry.

Just trying to understand what factors caused a difference in the vector copy number between the cells that are infused and what’s actually measured in the blood, aside from the percent engraftment, what other forces will cause a difference between those numbers?.

Thanks Josh. This is Philip. While I think – there’s a number of factors I think you’re aware of that impact the relationship between the drug product and the peripheral VCN as measured. Some of those include the absolute cell dose, was provided including, of course, as you point out the percentage of cells in that dose.

And a second feature that we’re much more about now are the quality of their cells, whether they have the phenotype required to be a true long-term primitive stem cell. And so I think those are critical and across program. And as you seem in sickle cell disease, clearly the disease status makes a big difference.

And our recent changes to include preharvest transfusions, we believe, make a big difference to the quality of the stem cells recovered as well as the ability of those cells to engraftment. So like many things, it’s complex. are But I think walk you through is a fairly set of changes that are trying to address each one of those criteria..

Josh, at the higest level – just to finish off, at the highest level, this is the part of the reason sickle cell we’ve been so actively trying to move from a bone marrow harvest apheresis to sort of almost a top line objective to really address any number of factors there.

And we’re certainly excited to see some of these data that allows us to dig into and understand a little bit more specifically, and maybe also start to see why the apheresis of thalassemia is more consistent in that regard. So that’s an exciting step forward..

And when you report peripheral blood VCN, what cells are you actually measuring and capturing in that assessment?.

So these are PBMCs basically. So it’s just a peripheral cells..

And does the successfully transacted peripheral blood cell have a survival advantage over an cell or is only the red cell that has that?.

Yes. So we don’t give another transgene, will not be active in any, I think, other than cell. We don’t believe there will be any difference in the marking in the peripheral blood versus the So that we think that should be a very good marker of bone marrow engraftment..

All right thanks you so much..

Thanks a lot Joshua.

Our next question comes from Eric Schmidt from Cowen & Company. Your line is now open..

Thanks for taking in question. Congrats on the study progress.

Maybe just to touch on a question that indirectly, do you think that age in sickle cell disease is a factor in driving better outcomes?.

This is Nick. I appreciate it. I think you’re asking us to speculate here. But maybe I’ll cautiously look over Mohamed here to see if he has some thoughts. But again, time will tell as we start to treat younger patients..

Yes. As Nick said, time will tell. I think we just don’t have that data for gene therapy. What we can say is, for stem cell transplant in general, in particular for patients with sickle cell disease is a huge difference between younger and older patients. And certainly, younger patients do much better with stem cell transplant.

But that is a different kettle or fish. So we will see how this evolves as we hopefully go into younger patients..

Okay. Then just for clarification, group C sickle cell patients treated with plerixafor. It sounds like we’re going to get several patients in vivo drug product VCN.

Is that correct at ASH but none of those patients have yet to be transplanted?.

Yes, the time of actually, you’re right, we will allow some drug product information but they will be at the in vivo data..

Have you treated any of the patients yet, Nick?.

I can’t really speculate on that. I won’t think much we’ll give a full update on where the study stands at the time of ASH..

All right. And I don’t want to lose focus on bb2121either. You talked about having additional..

Neither do we..

I know you’re going to have 6 months or so additional follow-up.

Are you going to include any additionally treated patients in that cohort? And what should we be looking for in the longer-term follow-up?.

Thank you Eric, so we’re – provided me – providing the update on the 21 patients that were in the sort of escalation cohort. And as you know, we have initiated the expansion cohort, but none of those patients will be far enough or long to provide any kind of detailed update.

So it will be a pretty significant update in the context of 6 more months across these patients to be able to understand everything from durability to response to safety. So on that sense, the good next look at the BCMA program. And both Celgene and us are very excited about that..

Thank you.

Thank you..

And our next question comes from Cory Kasimov from JP Morgan. Your line is now open..

Hi, good morning thanks form taking my questions and good to the progress across the entire pipeline. One question to follow-up on what Eric just asked about, group C the sickle cell trial. The abstract was as of July.

Can you say whether or not you’ve enrolled more patients than the 2 since that abstract?.

Again, let’s not if you don’t mind, let’s not speculate. We will provide an update at that time at ASH on the fullness of that.

One of the things that is and we know it’s across all our studies, given all these variables and the prior transfusions, et cetera, and the scheduling and so forth, the emphasis for is really trying to understand this data and trying to be able to with very few numbers understand where we want to go next.

So enrollment is you’ve seen the abstract, is proceeding. And so we will provide a specific update on that. But the overall emphasis is try to understand this data like we’re outlining here to say.

And we’ve got a and we’re starting to addressing challenge and do we see consistency if so, then what’s the appropriate and most aggressive path that we can from a regulatory point of view..

Okay, understood.

And then for the 2 patients that have been updated in the abstract patients 1312 and 1313, were they receiving regular blood transfusions prior to the required 2 months pre-infusion of LentiGlobin?.

No they were not..

They were not. Okay. And lastly, just quick one on the BCMA program.

For the 2121 study, the product, is this initial trial should we expected to look much like the bb2121 in terms of size and scope of that study?.

Yes, it’s very much modeled on the initial study with 2121..

All right great thank you..

Thanks Cory.

And our next question comes from Jim Birchenough from Wells Fargo. Your line is now open..

Hi, thanks for taking the question and congrats on the progress, Just wondering for patient 1313, is it possible to express their T87Q level as a percent of total hemoglobin, just so we can benchmark against the earlier results from Study 205?.

Yes, so certainly we will be doing that in the ASH presentation.

So it’s not in there. at this point in time. So we can’t really speculate on that Jim, at this point.But you can see, we shared it here the trajectory of it, but we’ll do the same as we’ve done in the past across the patients. You know the that will allow you to understand as a percent..

And then just on study 205, the second and third sickle cell patients seem to be on a relatively better trajectory than study 206 patients.

Will we get an update on those patients specifically? And anything you should – she can say about what our expectation should be for those 2 additional patients from Paris?.

I think the only we way right now, Jim, is the expectations, yes. we’ll provide an update on 204, 205 and 207 in all our studies, and in this case, the sickle cell patients certainly will update it as they are part of the 205 study. So can’t really speculate on that.

But I think well, we’ve been trying to highlight there is, those are obvious in patients who had the benefit of prior transfusions, and seem to be consistently doing better than those who did not. So again, we’re trying to out these variables.

And we’ll provide an update on that in the full context and also the additional follow-up on the group B patients..

Yes, it’s also of the 305 subjects were not treated with our refined manufacturing process. So we think that process is superior and will get different results..

And maybe just final question on the cell therapy side of the business it seems like you got some interesting preclinical data on and controllable cell therapies.

When should we see some of those moving into clinical development? When we might see bluebird move beyond BCMA for a cell therapy product?.

Philip, would you like to handle that one?.

So obviously, we’re beginning to show some of the preclinical data that we’re very excited about. As you pointed out both on use of editing and T-cells as well as controllable CAR T-cells using some drugs. Those are obviously exciting technologies. And as we approached the client with those, we’ll be sure to update..

Okay thanks for taking the question..

Thanks a lot Jim..

And our next question comes from Matthew Harrison from Morgan Stanley. Your line is now open..

I guess, first question, can you comment on how much additional follow-up you can expect to those 2 sickle cell patients? And then also, I think these 2 patients both had 2 doses of drug product. I think that’s different than what we see from some of the other patients. Can you just comment on the review there? And then have one follow-up..

So, Mohammed, you want to address those 2?.

Yes, I think the follow-up will be incremental. I think they can imagine probably in the next major time point for those 2 patients will be presented at ASH. In terms of the 2 drug..

It has to be – lets be more specific. One of the patients will be close to 2 months, one will be close to 2 months. Just to give a specific..

And then in terms of the 2 drug so actually the vast majority of the sickle patients have actually acquire 2 or more drug products derived from bone marrow. So in general, we have required multiple bone marrow harvest to achieve adequate cell doses for our patients. So this is very typical. And as you mentioned, one of them is to move into apheresis..

Got it. Perfect. That’s helpful. And then one question from apheresis process, I saw on the abstract that had a event after the apheresis.

Can you just comment sort of the clinical around that event? And if you think there is any relation to the apheresis process or not?.

Yes, so I think sticking to largely what’s in the abstract, this particular individual did have associated with bone marrow harvest. So it’s hard to speculate exactly what the mechanism of this was. But as we also highlighted in the harvest, they were numerous that in other patients post bone marrow harvest as well too.

So it’s very unfortunate frequent after cells..

Nothing new on the apheresis side..

Yes.

Perfect thank very much..

All right thanks Matt..

Our next question comes from Dane Leone from BTIG. Your lien is now open,.

Two from me.

The first one being, for the patients enrolled in the products for study, was there any on having a in the prior 12 months? And what is – can u be more specific in terms of what you’re looking for from the safety perspective that give you comfort to move it into the the format for the study?.

Yes, that was a good question. So I think, the first question, no. I mean these patients in plerixafor were general typical for our they had some of them lots of them prior to getting mobilized.

The only major difference is we this 2- month leading period of transfusions, which can be helpful at suppressing in fact, that’s one of the major reasons that was implemented was to suppress during this 2-month period. So that was the only in that respect. And then the second And then the second question, safety. So we’re looking for a safety.

So all safety we’re looking for safety. So all safety events, we were monitoring these patients for any potential complications.

Now most relevant, obviously, is the experience in which patients develop very significant increases in their white blood cell count and the life- threatening crisis after receiving And so were obviously very cognizant of what these patients white cell counts were doing and monitoring them for very severe And I can tell you that these that these patients – that this 1 patient did have that you commented on did not follow the criteria or follow the same as the GCSF.

And so, in your perspective, has this developing the clinical data and the formation of what you think will be an ideal protocol for sickle cell.

Can you can update us on your thoughts around what would be a clinical outcome measure the regulators or what you think clinicians would gravitate towards with these patients?.

This is Nick. Again, we really are trying to be cautious about not speculating. Once we have the fullness of the data here at ASH, we can a little more extensive conversation on that.

But again, part of this is aggregating just enough information then we can get a sense about how the different variables are behaving and the consistency of the outcomes through what ties to what, will allow us then to sort of get more specific around which of the various, call standard, but what are the various options of endpoints in pivotal study for sickle cell disease to engage in that debate first and foremost with the agency.

So too early to on that. But this is certainly a step in the right direction. Like a said earlier, we feel the agency has shown signs in sickle cell to be very open to engage on some creative options to really do the best we can for sickle patients. .

Thank you very much..

And our next question comes from Michael Schmidt from Leerink Partners. Your line is now open..

I had just a follow-up on the 2 sickle cell disease patients.

Remind me what the production was for Patient 1204 at 3 months? I think you said it was lower said it was lower than what you saw with this 1313 patient?.

Yes, marginally lower. So I don’t have it on top of my head, but approximately – it was probably about 20% less I think patient. .

All right.

And is it the absolute hemoglobin – hemoglobin production that’s important or the the relationship with overall HB levels?.

Well, the answer is probably bit of both. I think, obviously sickle cell anemia is at some level an anemia, an increasing level of globin is important to solve that problem. Then there is a problem of the sickle issues, and that is going to be corrected by having a substantial fraction of that globin being in nature.

So I think that we’re looking to achieve both. And as Mohammed previously said, we’re targeting around 30% or hopefully more but hopefully that will come with the correction of the total hemoglobin levels to a set point..

Sounds good. And then question regarding the medicine advanced therapy designation.

And I’m just curious what the impact of that is, and may how that might differ from something like a breakthrough therapy designation?.

Yes, I think this is certainly speaks to bluebirds very proactive strategy for engaging with regulators to get as much as frequent feedback as we can. And I think this is an opportunity for us really to engage more frequently with the FDA to get regularly feedback on what they think of our trial design and our potential endpoints. .

And one of the main emphasis here is try to obviously early dialogue, but also what’s the development path? How do you think about what should be registration study sort of, at what point or what time should? It’s pretty specifically.

The good news is, we really have had a very good relationship with the agency that does spectacular engaging with us across, whether it’s manufacturing or clinical. So this is certainly an important step. But I don’t think it fundamentally changes how we interact.

The key strategy that we have is, we like to have data before really engaging with the agency in a way. So we get to how to as supposed to here’s what to things going on and here’s what we think is the right path forward based on the data we’re seeing. So obviously this is a nice step in that direction. You’ll hear more at ASH.

And as soon as we can, we comment more specifically on how we thinking about U.S. and European development plans for sickle..

Great thank you..

And our next question comes from David Nierengarten from Wedbush Securities. Your line is now open..

I can ask a lots most here. But I’m actually curious about the CD34 cells in that CD34 phonotype.

First off, is it known in prior studies with plerixafor that it degenerates more primitive CD34 cells? And then, similarly on that that atypical CD34 patient from Northstar-2 that you look at those stem cells and where they again a different phonotype with – particularly, low number of or high numbers of the cells? Thanks..

This is Philip. starting at the top, we’ve on the research level have been very interested in understanding the phonotype of CD34 cells, and how that correlates with features such as engraftment, and ultimately in vivo VCN.

As you pointed out, I think the data that we have on comparison of bone marrow-derived stem cells and sickle cell disease versus apheresis is actually new. I don’t think there is other people have done that sort of study.

So I think that’s nothing to really reference to, although plerixafor is, of course, used usually in combination with GCSF and stem cell mobilizations. And one of the reasons that’s done is to improve both a number and quality of the stem cells in those standard mobilizations.

With respect to sort of the Northstar-2 subject, these are exactly the same types of analysis that we’re doing now across the board.

So we’re looking for the level of CD34 expression, which we think is a good characterization of stems that’s present in that cell population, as well as whether there are any definitive lineage expressed in those cells and you remember that we mentioned that type of analysis specifically with respect to the that Northstar-2 subject.

So this is all part of the same And I think it’s important to understand the drug product as well as we can to be able to predict the outcomes in patients across and sickle..

And David, this is Nick. The thing we’ve said, and it’s glaringly obvious right, is the major difference between and sickle is where we get the cells from. So this is why we spent so much time trying to understand this. And this is an unusual situation to be able to compare across both. So in that sense, I think it is new and also very interesting.

It really starts to speak to eventually being able to figure out how do you think about dose? And how is that different in bone marrow versus apheresis. And so having both sides to compare against is we’re going to be we think very meaningful in starting to unravel or unveil sort of more fundamental understanding of what’s going on.

So more to come on that, certainly as we continue to get more patient data be able to look across these variables. .

Okay thanks..

Thank you David.

And our next question comes from Matthew Luchini from BMO Capital. Your line now open..

Congrats on the progress, so three from being, so first on the plerixafor mobilizations side , looking at the 3 patients, notice that one, you got a little bit of a range, 1 patient slightly lower at 5.6 times kind 6 cells, and I was just curious if you could provide a little bit more color on this patient, if there’s anything that was different about him or her from a baseline point of view or the experience.

And then secondly, on patient 1312, obviously, it’s early here, but we’ve got peripheral VCN at about 2.6 copies for at 1 month.

I’m just wanted to hear from you a little bit of how you’re thinking of the significance of that time point? And maybe you can remind us where Patient 13 maybe even patient 13 were at that same time point?.

So Philip, you can address the first one, the variability if you will?.

Yes, with respect to plerixafor mobilization, obviously, we anticipate some variability from patient to patient. What I can say about that particular subject, which is in the abstract is will be the absolute mobilization in the peripheral blood was lower, and that obviously explains the harvest dose – the harvested dose was lower.

So it was simply that the drug didn’t mobilize as effectively directly in the patient.

With the – perhaps Mohammed wants to come out on the 1312 subject?.

1312 at one month. So it’s obviously an impressive in vivo copy number at that stage. And so I think that is certainly considerably higher than other. I mean, it’s safe to say that’s very promising because one of the major issues that we’ve had in 206 was some a suboptimal engraftment of our drug product transduced cells.

And so this patient definitely appears to have robust engraftment of the cells. And then – so as we’ve alluded in the abstracts and we stated before, I mean, comparatively speaking, this is a much better preservation of vector copy number that we’ve observed in the other 1206 studies and comparable to what we saw in 1204..

And even 1204 at this time point, Matt wasn’t even, I think just trying to engraft at that point. So in that sense, it’s really – It’s not even really a comparison. That’s what it’s a little tricky to look at the way we’re displaying this just because it’s at the last measurement, so it’s not – you’re comparing different time points.

But the point here is to same, where you sort of ultimately get to them. The fact is that these patients at 2.6 at one month is a little bit sort of almost off the charts..

Thank you. And our next question comes from Ying Huang from Bank of America. Your line is now open..

Good morning. Thanks for a taking a question. I have a one for sickle cell.

So you guys have done good job in terms of improving the VCN number in your products, but what are you trying to improve in terms of seeing a higher peripheral VCN number for sickle cell? And then at ASH, would you have already finalized the product bb2121, if that’s the case, would that include also patient within the instead of only patient in Phase I? Thank you..

So, thank you. Can you address the second question there. We will provide an update at ASH on the study I outlined. As far as the development plans and where we go with early launch treatment, that will be for another time.

So we’re certainly actively discussing and debating what the data merits in our dialogues with who is obviously involved and big pieces of that program. So on the first question there, I think Mohammed you can hit it, but it really hits all the key points that we’ve been addressing today..

Yes, no, I mean I think it’s – to summarize sort of what was discussed, I think in terms of addressing the loss of vector copy number going from the drug product to I think certainly one thing we can do is increase where we start from, so that we have a better peripheral vector copy number.

We’re trying to increase the cell dose, so hence the plerixafor mobilization is we hope huge step. We’re trying to increase or improve the purity and the stem-like nature of the drug product, and hence, again, the plerixafor mobilization will be helpful.

We are trying to both reduce inflammation in the sickle bone marrow as well as to optimally for reception of the transduced stem cells. And hence we implemented the two months prior transfusions and made the myeloablation more rigorous..

So overall, it’s just a – It’s a combination of all these factors. Exactly what the contribution of each one is effectively do the and then thought try to reduce the slope. And that’s what I think we’ve seen a step towards here..

Thank you..

Welcome.

Thank you. And our next question comes from Vincent Chen from Bernstein. Your line is now open..

Thank you for taking my questions and congratulation on the progress. Couple of questions on the plerixafor mobilization. First, the VLC the plerixafor patient, in the sense this is related to plerixafor mobilization, is there a world where he might consider moving to a lower dose.

Either that can potentially require multiple rounds of apheresis or plerixafor mobilization? Also were patients transfused prior to the plerixafor? And what level of hemoglobin S did they have prior to receiving plerixafor treatment? And then I have a follow-up..

Yes, so answering the first – the second question first.

So I think our goal, and I think this is based on extensive discussion with people who do this is, to get the hemoglobin S down below 30%, and so this patient was and all of our patients are transfused to get the total hemoglobin F below 30% prior to beginning the process to minimize the probability of crisis.

As to the speculation of what causes patient to have a crisis, the is too complicated necessarily to come up with a answer here, speculative. All we can say, this patient did also a crisis after their bone marrow harvest..

I think that’s an important point here. we then view this not as the data safety monitoring board, we view this as of any significant in that regard. Because it was not something that was unique to the apheresis per se. It’s also something.

Remember we’re doing both of these treatments on these initial patients because the apheresis on was really a research purposes and safety purposes. So that’s from our perspective was not something that got in the way of us moving forward..

I see. That’s great.

And then with respect to cell quality, how do cells generated from apheresis compared to the bone marrow harvest in terms of some of the other commonly applied assays, for example, their ability to reconstitute marrow in human model or differentiation assays?.

This is Philip. So there is a fair amount of history on plerixafor-mobilized stem cells. And the short answer is on those publications, they behave very similarly to other standard methods of mobilization. So and of course, plus plerixafor. So there’s really – we don’t believe this process is a substantially different.

So I think that’s probably the most important feature. So from a apheresis perspective, I think that this specific way of mobilization I think has great promise and we’ve shown that in this sickle population that’s really the new piece..

Thank you very much and congrats again..

Thank you very much appreciated..

Thank you. And our next question comes from Biren Amin from Jefferies. Your line is now open..

Yes. Thank for taking questions.

Did patients for 1312 and 1313 have a of change similar to Patient 1204?.

Not to our knowledge. This has not been documented..

And so how do you think the sickle cell patients with thalassemia would compare to patients that don’t exhibit this trait?.

It’s an interesting question. I mean, I think the short answer is, we would have to actually have a reasonable number of patients with this to really make a definitive statement. Yes, I think that’s about..

I can’t really speculate on that, Brian. We need more data on understand the of that..

And just on the license insurance program, what’s the thought on how that would be strategically positioned compared to LentiGlobin?.

Yes, I think our focus here has been around do everything we can to leverage the platform that we have and the technology that we have in places as Philip outlined. So we are to some degree sort of agnostic about how we do it. So we want to really do the best we can for sickle cell patients.

So when we saw his opportunity here with actually one of our already on the program and broadly speaking, we thought ti was an exciting approach. And so wanted to take a look at it. And as Philip just outlined, some of the data here is actually pretty exciting.

So at the end of the day, there is to have more sort of options for sickle cell is our objective here. And ultimately, how these play out, we’ll have to see if they are completely data-driven. For right now, we’re certainly full speed ahead on both..

Awesome, thank you..

Welcome. Thank you..

Thank you. And our last question comes from Huidong Wang from Barclays. Your line is now open..

Thank you for taking my question.

So I know it’s still evolving, but just wondering if you have any sense like what would be the peripheral VCN you’re looking for that will be a good indication for benefit?.

Yes, I mean, I think – this is Philip, so obviously we’re – that final number is going to be data-driven based on what we actually see. But we’ve certainly had a goal trying to get into that 0.5 VCN and above range. And so far that’s been – at least been the goal.

But obviously with the final target, if you will, is going to be driven by the and the relationship with that VCN number..

Yes, this is Nick. It’s also may vary a little bit from thalassemia the sickle cell, and obviously may vary in between. The hope is that we can consistently get above the threshold that we’ll deliver an important outcome for all the patients. But it’s too early to speculative what exactly that number is.

But the good news is, our ability to deliver consistently higher and higher and higher is something that we think is a very good thing..

Great. And I have one question regarding the in sickle cell. So how do you see yourself compared to the competitors in this space? I know there are two independent programs will go to clinic later this year.

If you can give some thoughts?.

Yes, so just to be clear, the program that we talked about that regulates in program. So there is technology. Although it hits the same target as many of the gene editing companies regarding which is I think that the editing approach is interesting in the sense that they try and achieve a similar outcome.

They try and introduce which drive a HPA phonotype. The challenge that the editing approaches have is creating sufficient number of the desirable mutations that drive that outcome.

So every in the cell is if you will fully penetrant to completely changes the biology of that cell, every mutation you make in a gene has to be the right mutation before it actually drives the phenotype you’re interested in.

I think that’s one of the reason we’re seeing the 70%, 80% change versus the 30%, 40% has been reported by the gene editing community. So we think that program is very competitive.

We’re also obviously very interested in gene editing And we have approach, which we think has advantages both in terms of specificity and in terms of how easy it is to deliver this single cells. And that we’re working on that too. But for today’s abstract to see if LentiGlobin program that we’re highlighting..

Thank you..

Thank you Huidong..

Thank you. And I’m showing no further questions in the queue at this time. I’d like to turn the call back over to speakers for any final remarks..

I just want to thank, everyone, for taking the time. And obviously, if you have any follow-up questions, we’d be happy to take them at any point, just reach out to my cell and we will respond. Thank you very much..

Ladies and gentlemen, this does conclude your program for today, and you may all disconnect. Everyone, have a great day..