Manisha Pai - Senior Director, Investor Relations Nick Leschly - Chief bluebird Dave Davidson - Chief Medical Officer Rob Ross - Head of Oncology.
Josh Schimmer - Piper Jaffray Ying Huang - Bank of America Whitney Ijem - JPMorgan David Nierengarten - Wedbush Securities Debjit Chattopadhyay - ROTH Capital Partners Jason McCarthy - Maxim Group Wendy Lam - Oppenheimer & Co. Gena Wang - Jefferies & Company Jeff Chen - Cowen and Company.
Good day, ladies and gentlemen, and welcome to the bluebird bio, Inc. ASH abstract release conference call. (Operator Instructions) As a reminder, this conference is being recorded. I would now like to introduce your first speaker for today, Head of Investor Relations, Ms. Manisha Pai..
Thank you, and good morning, everyone. This morning we issued a press release announcing six presentations of bluebird bio clinical and preclinical data at the American Society of Hematology, or ASH, Annual Meeting. The press release summarizes the preliminary data that will be published in abstract form on the ASH website at 9:00 O’clock AM today.
More complete updated data will be presented at the ASH Annual Meaning on December 5 and December 6. With me on the call today with prepared remarks are Nick Leschly, Chief bluebird; Dave Davidson, Chief Medical Officer; and Rob Ross, Head of Oncology.
Jim DeTore, Chief Financial Officer and Jeff Walsh, Chief Operating Officer are also here today and will join us 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, it should be noted that the data for LentiGlobin, announced in the ASH abstract, are preliminary in nature and the Northstar HGB-205 and HGB-206 studies are not completed. There are limited data concerning long-term safety and efficacy following treatment with LentiGlobin.
These data may not continue for these subjects or be repeated or observed in ongoing or future studies involving our LentiGlobin product candidate.
It is possible that subjects for whom periodic transfusion support has been reduced or eliminated may receive transfusion support in the future and that subjects with severe sickle cell disease may experience serious symptoms of the disease.
Additional information concerning these risk factors is contained in our filings with the SEC, which are available on the Investor Relations section of our website, www.bluebirdbio.com.
While we may elect to update forward-looking statements in the future, we specifically disclaim any obligation to do so, 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.
Before we begin our prepared remarks I would like to note that we have a set of prepared slides for this event, which you can access now by going to the Investors section of the bluebird bio website. The agenda for today's call is as follows. Nick will make some introductory remarks.
Dave will then review the LentiGlobin abstract data followed by Rob who will discuss our oncology abstract. Nick will then conclude and we will open the call up for Q&A. Let me now turn it over to Nick..
Thank you, Manisha. Good morning, everyone and thank you for joining us on the call. bluebird is and always will be a purpose and patient-driven company.
As pioneers in an emerging field, we are focused on the longer-term view of delivering value to our shareholders by delivering truly transformative therapies to patients with debilitating or life-threatening diseases.
On that front, we are encouraged by what we are learning from our brave clinical trial patients about how our platform can potentially transform the lives of patients suffering from beta-thalassemia, sickle cell, ALD and [indiscernible] cancer.
Although it will not be the focus of this call, our belief in the emerging pipeline and next-generation programs from our leading core gene therapy platform is very strong.
We believe our relentless commitment is never good enough, coupled with our strong fundamental translational platform will be our biggest source of sustained competitive advantage. We expect this to become clear over time, as we consistently learn from our data, innovate and deliver even better products back to the patient.
Let's now turn to the ASH abstract data release. As is bluebird tradition, we are going to be direct about what we know and what we do not know. Abstracts only tell a preliminary part of the story, but there are some important pieces of information for us to share and discuss.
One upfront caveat, it is best for all of us that we do not speculate, as we are working from the early and limited data in the abstracts but we will provide the most thoughtful data-driven answers that we can with more data and discussions to come at ASH.
First, on the beta-thalassemia front, patients are starting to sort by genotype, reflecting the amount of T87Q that is likely required to impact their disease. Remember, T87Q is the engineered beta-globin that is a product of our gene therapy.
Patients as of the abstract date with non-beta-0/beta-0 genotypes are 100% transfusion independent, some out to 18 months. We believe that these genotypes represent approximately two-thirds of the addressable thalassemia major population in the US and Europe and we are excited to have such strong results to date in this population.
Among the patients with beta-0/beta-0 genotype, who produce no endogenous beta globin, have had a reduction in transfusion need but none have achieved sustained transfusion independence. In sickle cell disease, the initial patient treated in HGB-205 is producing 51.5% anti-sickling hemoglobin and doing well.
It is very exciting for us to see this and more importantly, it is good to know that this 13-year-old boy is living his life without transfusions or hospitalizations for his sickle cell disease. The HGB-206 abstract reflects the very early stage of this study, particularly at the time the abstracts were submitted.
However, the study is enrolling well and we did announce yesterday in our quarterly results that we are proactively expanding the study to 20 patients to get more data sooner and have flexibility on the regulatory options and timeline.
From a platform-wide [ph] perspective, we are pleased to see our median production of T87Q in patients of all genotypes in the Northstar study at 5.2 grams per deciliter with T87Q representing substantial portions of the total hemoglobin level in these patients. Last but certainly not least, our oncology franchise is emerging more publicly.
Our anti-BCMA CAR-T program partnered with Celgene and targeting multiple myeloma is on track to enter the clinic in early 2016. The abstracts at ASH start to frame out why we believe we will not only be a participant but a leader in the oncology CAR-T field.
Before Dave and Rob give you some more detail on the abstract data for LentiGlobin oncology, I went to skip a few steps and proactively highlight a few questions that we think are logical to ask. We have listed a number of them here on this slide.
Many of these questions will be covered by Dave and Rob, some of the questions are simply too early for us to provide a useful answer. In particular, it is too early to discuss the full data that we will be presenting at ASH.
It is also too early to discuss the clin reg path of LentiGlobin in detail until we have seen more data in more patients with longer follow-up and have had the appropriate interactions with the regulatory agencies. Finally, let me be clear about bluebird's mindset.
We are committed to bringing LentiGlobin to all patients who can benefit from it regardless of genotype. This commitment to patients is why we have built such depth inside our company to continually learn, innovate and improve. With that, over to you, Dave..
Thank you, Nick, and thank you all for dialing in this morning. As Nick mentioned, we have made tremendous progress on our clinical programs over the past two years and we are optimistic about what lies ahead.
We are still early in the LentiGlobin clinical development process and there is still more to learn about the variables that determine clinical success.
The highlight of the emerging clinical data as of the July 31 abstract data cutoff is that transfusion independence has been achieved in all of our beta-thalassemia major patients with non-beta-0/beta-0 genotypes who have been followed for six or more months.
All six of these patients remain transfusion free as of the date of cutoff with the first treated patient now followed for 18 months in the 205 study. In the Northstar study, we saw similarly impressive results among non-beta-0/beta-0 patients with 287 days being the median number of days of transfusion independence and a range of 171 to 396 days.
These promising results are being driven by robust production of T87Q with a median level of 5.2 grams per deciliter and a range of 1.9 grams per deciliter to 8.2 grams per deciliter in Northstar patients of all genotypes monitored for six months or more after treatment.
T87Q levels in the two beta E/beta-0 205 study patients are both high at 7.8 grams per deciliter and 9.7 grams per deciliter at 18 and 15 months of follow-up respectively. Patients with thalassemia due to beta-0/beta-0 genotypes are also producing substantial amounts of T87Q, which is an important observation from these first clinical studies.
And early data indicate a reduction in transfusion requirements but not sustained transfusion independence to date.
It must be reiterated that all of the thalassemia subjects in our trials have the most severe form of the disease, beta-thalassemia major, and are transfusion dependent when they enter the study requiring eight or more blood transfusions per year.
Regardless of specific genotype, this heavy transfusion dependence results in iron overload and potentially lethal organ damage such as heart and liver failure.
The results showing differing outcomes based on genotype are expected given that beta-0/beta-0 patients produce no functional beta globin and therefore require larger amounts of T87Q to achieve transfusion independence.
In contrast patients with beta E or beta plus genotypes produce variable amounts of beta globin that contribute with T87Q toward reducing the hemoglobin deficit required to achieve transfusion independence.
Further follow-up is required to fully assess the correlation between genotype and degree of clinical benefit as well as to define the other determinants of clinical outcome.
Importantly, for sickle cell disease, it is expected that only relatively modest levels of T87Q production of approximately 30% of total hemoglobin translating to around 3 grams per deciliter should yield meaningful clinical benefit based on observations showing the therapeutic effect of increased fetal hemoglobin expression.
The clinical value of transfusion independence is self-evident, but there is also benefit from reducing transfusion requirements in patients. However, at this time, it is premature to talk about the relative clinical value of differing degrees of transfusion reductions and how these might influence the regulatory path forward.
We will be able to share more data next month at ASH that will serve as a better foundation to discuss our development plan. Turning now to sickle cell disease, in June of this year, we reported on the first patient with sickle cell disease ever treated with gene therapy, a participant in the 205 study.
At that time we were pleased to report that this patient was producing 45% anti-sickling hemoglobin after six months of follow-up, of which 40% was T87Q. Our 205 study abstract provides additional data up to nine months in this patient.
And it is gratifying to see a continuing rise in anti-sickling hemoglobin to 51.5% with T87Q production now representing 48% of total hemoglobin. Most importantly, the patient has remained free of transfusions and sickle cell-related complications.
Also in June we announced that we had treated the first patient in the 206 study in severe sickle cell disease. The abstract from the 206 study has been accepted for a poster presentation at ASH. At the time of abstract submission, it was too early to include any meaningful clinical data.
At ASH, we will provide early data on the first few patients in this trial at which time the duration of follow-up will be limited. This is consistent with our expectation that a more complete picture of the results for LentiGlobin in sickle cell disease will play out in 2016.
We are pleased with the pace of enrollment in the 206 study to date and we will provide an update on enrollment status at ASH. We announced yesterday in our quarterly results press release that we are increasing the sample size of the 206 trial from eight patients to 20.
Our decision to expand the study will allow us to gather more comprehensive data about our product and will provide increased flexibility and regulatory options in the future. The safety profile of LentiGlobin remains favorable and is consistent with autologous transplantation.
As of the July 31 data cut-off, there were no grade 3 or higher drug product-related adverse events or evidence of clonal dominance. In short, we remain excited about the transformative potential of LentiGlobin for patients with beta hemoglobinopathies and the emerging clarity of our data to define a path forward.
We look forward to providing updated data in one month at ASH that can serve as the basis for more substantive discussions of our plans for 2016 and beyond. Rob will now take you through bluebird's oncology abstracts at ASH..
Thank you, Dave. Our portfolio framework has two pillars with severe genetic diseases on one side and T-cell immunotherapy on the other. In 2015, the T-cell immunotherapy strategy has begun to crystallize to those outside bluebird, as evidenced by our partnerships with Celgene, Kite and Five Prime Therapeutics.
We believe strongly in the unique science and translational gene therapy platform that we have built and that our Lentiviral genome editing and cell therapy translational platform make us a partner of choice for others with cutting-edge technology applicable to immuno-oncology.
The three oncology abstracts at ASH this year, all three presented by members of our own in-house bluebird scientific team, demonstrate the robustness of our T-cell immunotherapy translational science.
These three abstracts cover critical research, translational and CMC aspects of our T-cell oncology pipeline, including demonstrations of the strength of our T-cell manufacturing platform and non-clinical in vitro and in vivo data on our lead oncology candidate, bb2121 partnered with Celgene.
Bb2121 is our CAR-T product candidate targeting BCMA, or B-cell maturation antigen, which is highly expressed on malignant plasma cells in multiple myeloma. Because BCMA expression is largely restricted to plasma cells, we expect that similar to targeting CD19, there may be little off-target toxicity to essential organs.
In the T-cell oncology space, there has been significant interest in approaches that generate younger T-cells as a method to improve the risk-benefit of these treatments and the potential durability necessary to tackle the persistent threat of tumor recurrence.
To date, many approaches to achieving this goal have involved cumbersome and costly manufacturing changes.
At ASH, we will discuss an important observation made by our scientists demonstrating that by culturing our anti-BCMA CAR-T cells with a PI3-kinase inhibitor, we have produced a product that has many properties associated with the younger T-cell subset.
Consistent with the younger T-cell phenotype, our team further shows that this product has improved in vivo efficacy and persistence in multiple-model systems. We believe this approach may have applications beyond just BCMA and could apply to the broader CAR-T universe.
We look forward to sharing more data from all three of these abstracts with you in December and bringing bb2121 to the clinic in early 2016. With that I will hand it back to Nick to wrap up..
Thank you, Rob. The data we have discussed today are still early and they are several months out of date already. We are planning an analyst and investor event at ASH where we will take you through the most up-to-date data set.
Also at ASH we will share a bit more of our oncology and R&D strategy, as we continue to broaden and deepen our efforts to build the company for the long-term. With respect to the questions I outlined at the beginning of the call, I believe we have covered most of them but at the risk of some redundancy let me briefly review.
Are you surprised by the genotype split in thalassemia? Not really, it has been very clear that the beta-0/beta-0 genotype produces no endogenous beta globin making it the highest clinical hurdle for T87Q production.
That said, we freely acknowledge that it would have been great to have every patient, regardless of genotype, become transfusion independent out of the gate but that is not the case. So there is more work to be done to best serve all patients.
Are non-beta-0/beta-0 patients less severe in their disease? All of the patients in our studies are thalassemia major patients, which means they are all dependent on transfusions and all have severe disease.
What happens with your clinical and regulatory paths now? We are really pleased to see clear consistency in the result among non-beta-0/beta-0 patients, not only for medical reasons but also for development reasons. It is too early to say more in the absence of full data and we do not comment on regulatory discussions.
That said, our overall regulatory strategy for pursuing accelerated approvals remains unchanged. We will share updated data at ASH in one month and we will discuss more about our development plans in the full context of the data.
What is the size of the beta-0/beta-0 population? The thalassemia major population, defined as patients who are dependent on transfusions, represents 60% to 80% of the symptomatic patients.
Although the genotype breakdown percentages are hard to know exactly and it varies greatly by region, our initial market research suggests that non-beta-0/beta-0 patients make up approximately two-thirds and the beta-0/beta-0 genotype represents the remaining one-third of the thalassemia major population in US and Europe.
What is the value of transfusion reduction? There is certainly clinical value in transfusion reduction and we need to further understand LentiGlobin's effect on beta-0/beta-0 patients in this regard. In short we need to see more and then assess the best path forward.
What are you doing to improve your platform? We are always working to improve our products and the platform. Our team has been proactively pursuing near- and longer-term ways to improve the value of our products to patients. The PI3 kinase oncology abstract is an example of the next generation work we are doing in oncology.
And on a more fundamental level, we have significant efforts in every aspect of our process, including ways to enhance vector copy number and cell transduction. Right now it is too early to discuss details or timing of these efforts but we are confident in the ability of our R&D team to deliver.
What affect does this have on your launch strategy? We are not altering our ongoing efforts to build internal capabilities for a potential commercial launch in thalassemia major.
How does this update relate to the LG001 patient data you announced two weeks ago? The presentation that Professor Marina Cavazzana gave a few weeks ago at the Cooley's Anemia Foundation Symposium discussed a patient who was treated eight years ago with our first-generation vector in the LG001 study.
This patient has a modest but sustained vector copy number that produced approximately 3 grams of T87Q for many years leading to seven years of transfusion independence but with the total hemoglobin that was often close to the edge of needing a transfusion.
We recently experienced - he recently experienced clinical symptoms of anemia, specifically fatigue, and received two transfusions. It is important to note this is not about persistence of the gene therapy in this patient, as vector copy number and expression of T87Q has remained largely unchanged.
As you know, we have since made critical improvements to the vector and our process that has led to substantially improved product as the data today outlines. How should we think about the sickle cell disease data? Our goal for sickle cell disease patients is for T87Q to exceed 30% of the patient's total hemoglobin.
It is early but we are excited that the continued data on our 205 patient with sickle cell disease show he has now 48% T87Q after nine months of follow-up. At ASH, we will provide early data on first few patients in the 206 study, so the follow-up will be short.
This is consistent with our expectation that LentiGlobin in sickle cell disease will play out more in 2016. In closing, it should be clear that we will stay the course of all of our programs and do it the bluebird way, with openness, transparency and unwavering commitment to bringing potentially transformative treatments to the patients we serve.
As you all know, we never speak about the company without reminding, not only all of you but also ourselves, of why we do what we do. Ethan, and patients like him who suffer from terrible diseases are often - are both our inspiration and our sobering reminder to keep working smarter, harder, faster to surmount the challenges in our path.
We are here to turn hope into reality for patients. To us this is what it means to be true blue.
Operator?.
Question-and:.
Yeah. (Operating Instructions) And I’m showing our first question or comment comes from the Josh Schimmer with Piper Jaffray. Your line is now open..
Thanks for taking my questions and for doing the call.
Just first to quickly clarify, I guess the press release says one of the two patients [indiscernible] transfusion independent, can you just clarify?.
Go-ahead, Dave..
Yes, Josh, this is Dave. So you are referring to the beta-0/beta-0 subject, is that correct? Yes, so, all of those subjects have received blood transfusions..
Okay, what was the mag - or do you have an estimate of the magnitude of reduction in transfusion seen in those patients?.
Yes, we can't address that at this time. We will be able to provide more information at ASH. We can only speak what is in the abstracts right now..
Okay.
And so, did you indicate the amount of T87Q specifically in those two patients? And how do you know that this is as much a reflection of the severity of these patients as opposed to maybe the release criteria of the vector copy number that - and the cell dose that they were given?.
Yes, so let me address the first part of the question first. So we have aggregate data in the abstract covering all of the genotypes.
And the aggregate data is a median T87Q level of 5.2 grams per deciliter and a range of 1.9 gram per deciliter to 8.2 gram per deciliter [indiscernible] variation that does exist but the exact details of that and what variables are driven by what will remain to clarify with further data and further follow-up.
And we can address some of those issues and more detail at ASH..
So but - how are you confident that this is a reflection of the patients as opposed to the release criteria in the vector copy number?.
Yes, so, we did address the range of vector copy numbers, which are good vector copy numbers. We know physiologically that the beta-0/beta-0 patients represent the highest hurdle in terms of achieving a total hemoglobin consistent with transfusion independence because they are making no endogenous beta globin.
And so, that is probably the fundamental driver of the observation..
And then one last question and I will hop back out.
Is there any relevance or how do you think the beta-0/beta-0 experience reads through to the sickle cell experience? Should we be concerned that there will be some sickle cell patients who have too severe a phenotype for whom the LentiGlobin profile will not be adequate?.
This is Nick, Josh. I think it is too early to tell on that, but I think they're sort of different. We have said that - we’ve stated that the 30% hurdle is what we are looking at for the sickle cell disease population.
So the 00 hurdle in thalassemia, I think they're a bit apples and oranges, it may still come down to some fundamental questions around how much beta 87 you can produce certainly consistently in the context of all the patient variability, et cetera. But I don't think that there is, at this point, a connection that we can speak to.
As we get more of the data put out maybe we can have further discussion on how things relate..
Got it. Thank you..
Thanks a lot, Josh..
Our next question or comments comes from Ying Huang with Bank of America. Your line is now open..
Hi. Good morning, guys. Thanks for taking the question and thanks for the updates.
First of all, have you looked at the time it takes for the patient to require a transfusion among those three beta-0/beta-0 and if there is any correlation between the vector copy numbers in those patients and the transfusion? And also does that relate to their prior transfusion requirement or not? And then secondly, do you think maybe a booster could actually help those patients? And then lastly I guess, what is your thoughts on the expansion of the sickle cell [indiscernible]? Is that coming from the suggestion of regulators? Thank you..
So, let me cover the last one first, this is Nick, and then Dave can chime in as needed. The expansion, no, that is something we proactively did. It's not a request from the agency. We did that, as Dave highlighted, as an effort to understand more and get more data on patients as well as make sure we have regulatory flexibility as we see the data.
And some great questions you had upfront on time, copy number and prior transfusions. That detail is not supplied in the abstract and there will be more data that comes at ASH and then I think we can come back to that set of questions. As it relates to a booster, I don't think there is much to comment on there.
That also is something that we can discuss further at ASH. But right now, as you know, that is not the overall strategy. We are looking at a one-time potentially curative therapy and that is our goal..
Okay, thank you..
Thank you, Ying. We appreciate the questions..
Our next question or comment comes from the line of Cory Kasimov with JPMorgan. Your line is now open..
Hi, guys, this is Whitney on for Corey.
So I guess understanding that obviously we will get a lot more data at ASH, I guess is there anything you are seeing in the beta-0/beta-0 patients that makes you think you could still reach transfusion independence there? Or is it just that maybe with the current product or something that is just not going to be a possibility in those patients or I guess any other color you can give there..
Yes, good question, understandable question, Whitney, but unfortunately that will call us to speculate and I think it is just too early.
I think what we do want to take a look at, all of us together when we look at the data at ASH, is understand at that time point where the patients are with beta 87, with expression and the copy number, etc., and then we can consider that.
We certainly - as we stated, both transfusion independence and also transfusion reduction hold clinical value but the devil is in the details on that, we need to understand that and see it play out over longer periods of time. And then also consider that in the context of sort of the risk-benefit.
There are others out there who - their sole focus is on transfusion reduction at pretty modest level in the order of 33%, etc. So I think there is a pretty clear statement of value there but how we actually play that out that remains to be seen.
But we are certainly very much focused on delivering value to the 00 patients now and also as we continue to improve our platform..
Got it.
And then in sickle cell disease, is there anything you can say about the baseline characteristics of the additional patients that were treated in 206 relative to the 205 patient? Were they also transfusion dependent or I guess any color you can give there as to how they might compare?.
Yes, I apologize, Whitney, we have to really stay focused on what is in the abstract. So whatever is in there and the answer to that question is not in there, so there will be more color as we get to ASH..
Understood. Thanks for taking the questions..
You bet. Thank you, Whitney..
Our next question or comment comes from the line of David Nierengarten with Wedbush Securities. Your line is now open..
Hi, guys. Thanks for taking the question. I had a couple questions on the beta-0/beta-0 patients.
First, if you could provide any detail on when the two patients had their transfusion, whether it was in 30 days, 60 days, 90 days kind of deal? And then the one that remains transfusion dependent, if there is a definition of that, have they received multiple transfusions or is it because they have had to have a transfusion but there has only been a month or two of follow-up? Thanks..
I don't believe, Dave, this is - I apologize, I don't believe we can comment on that just yet. Obviously a good question but - and we certainly will provide more color on two or three of those questions when we get to ASH..
Okay, all right. Thanks, guys..
You bet..
Our next question or comment comes from the line of Debjit Chattopadhyay with ROTH Capital. Your line is now open..
Hey, good morning and thanks for the question here. So, just from a regulatory clarity, I believe that is a reduction in transfusion - reduction in the number of transfusions and not transfusion independence.
So should we think about this kind of sort of a split label that beta-0/beta E to be evaluated separately versus beta-0/beta-0 or how should we think about your studies going forward? Do you think you will enroll beta-0/beta E and beta-0/beta-0 together or it will be split up into two different studies just from a regulatory standpoint?.
This is Nick. Debjit, it's a great question and certainly a very important one. I think what I will highlight here is that the data is just a little too early to draw those types of conclusions. We clearly need to understand a little better. We are excited about the clarity of the data that we are seeing in the non-beta-0/beta-0.
But what might be helpful to get at what you are saying here is Dave will just outline and frame a little bit about what the options are. They are fairly obvious, but they certainly are ones that we are considering very actively..
Yeah. Hi, Debjit. So, the course you raised is certainly a possibility but I think that is going to be dictated by more data as it matures and that will determine which path we take. Certainly there is the option to continue with all genotypes in one trial focusing on the different endpoints of transfusion reduction versus transfusion independence.
If there is a very clear emergence of a genotype base difference, the strategy you mentioned of separate regulatory paths based on genotype is certainly an option. And that has been followed of course by other companies with other therapeutics.
And ultimately you are looking for a very consistent and clinically meaningful treatment effect in a defined patient population. So as the data emerge, we will follow the most logical path..
Great. And then the three patients with beta-0/beta-0 genotype, they have varying responses, one being totally transfusion dependent versus the other two needing one transfusion.
So is there a - was there a big difference in the baseline characteristics in terms of age and everything else? Or - I am just trying to go in toward thinking about maybe some sort of a biomarker strategy where you can identify patients who are most likely to respond or is that too premature at this point?.
I'm going to jump in before Dave gets that. I think it is a very good discussion and I can see Dave is eager to actually engage in it. But I think it is much better to engage when we actually have sort of the fullness of the data in there.
But right now what we are seeing is that one step above, which is a split by - at least by genotype, right, at that level which comes back to the level of endogenous production.
Now, as we get sort of one or two layers below that and we understand what the impact and the variability are for maybe other reasons, then we can get to maybe some of the things that you are referring to. So apologies, Debjit, I don't think we can dig into that any further than that..
Just one more follow-up then. At this point you are not enrolling pediatric patients.
Is there any data to suggest that pediatrics are going to respond better than the adolescents or adults?.
Yes, Debjit, it is Dave. So in the French trial, we are able to enroll pediatric subjects. In the US studies, we recently noted that we were opening 204 to adolescents but not to younger patient populations yet. What we do know is that with regard to the rigors of the transplant process itself, pediatric patients tend to sail through that.
And of course pediatrics have less disease burden as well in terms of cumulative organ damage from the disease. But other than that it is really early to speculate about relative outcomes in those age groups..
Thank you so much..
Thank you, Debjit..
Our next question or comment comes from the line of Jason McCarthy with Maxim. Your line is now open..
Questions I wanted to ask have been answered. I just want to jump just briefly over to the CAR-T side, it hasn't been talked about yet.
If you are going to use the PI3-kinase inhibitors in your culture to make younger more active T cells, is that going to have an influence on the dosing in your clinical trial when you do announce it? Or I guess in other words, have you seen differences in cytokine release syndrome in your preclinical models that may influence how you move forward as you move towards the clinic in 2016?.
Terrific, this is Rob. I am glad to talk a little bit about oncology, that is awesome. It's a really good question, but one that we - one that is hard to answer because there are not good non-clinical models of cytokine relief. So it is very hard to do any more than speculate about the potential.
We certainly agree with your underlying thesis that if you have a younger more active or more potent T cell that you may have a different dose response. And in that setting the hope would be to be able to treat with a lower dose. And one could speculate, but it would only be speculation, that that might be associated with a different safety profile.
That is as far as we can go now but that is certainly part of the promise of generating a younger T cell, which has been an important goal in this field not just for us but for many of the academics and companies studying CAR-T cells..
And using PI3 kinase inhibitors for multiple myeloma in particular, is this a major part of the attraction from the partnership with Celgene because they are so active in that space? And with using bluebird's gene editing technology to make CAR-Ts and then kind of bringing in myeloma PI3 kinase inhibitors from Celgene, was that part of the basis of the relationship and the commitment towards going towards multiple myeloma?.
Hi, Jason, it is Nick. No, I don't think I would characterize it that way. We have a pretty long-standing relationship with Celgene and I think their focus is that we just drive hard at the science and that is what we have been doing for a number of years.
This is a piece of it, there is quite a bit more that sits behind or below the watermark at this point. So, I wouldn't characterize that as a driving force, but it is part of it and we are thinking about this and our effort is here in a very long-term way.
And so, that is how I would better characterize it as opposed to some sort of particular linchpin in our relationship with Celgene..
All right, great. Thanks, guys..
Thank you, Jason. Appreciate the questions..
Our next question or comment comes from the line of Wendy Lam with Oppenheimer. Your line is now open..
I have a couple of questions here first to Northstar. So, for a patient on 106, we know that that patient was transfusion independent after last year's ASH readout.
So I know that we may have to wait for the ASH presentation, but can you tell us roughly when that patient first - or when that patient required the first transfusion after being discharged? And then regarding LG001, one of your competitors mentioned that that patient in that study showed an increase in the proportion of cells with vector integration within the [indiscernible].
So I was wondering if you can give us a more details on exactly what was in this patient, what percentage of poly 2 expanded clones were seen and which cell types were - was this integration most prominent?.
Hi, this is Nick. Thank you, Wendy, for the questions. So I will handle the first one because we can't answer it, so an MBA can answer that one. We will of course provide more color on that, but as far as specific timing and so forth, that is not in the abstract. But certainly as we outline the details across the study that will become clear.
As it relates to the LG001 study, I will ask Dave to just comment on that because there certainly is - it is important to clarify..
Yes, Wendy, just at a high level, it is important to remember that the level of gene marking in this patient to start with is relatively modest.
And so, when we look at the individual clones and their proportion of the sort of marked cell population, it represents, even the most abundant of those, a small proportion of the overall sort of nucleated white cell compartments.
And so, the issues raised by others about does this represent some sort of concerning clinical observation, no, that is unlikely. This appears to be more just kind of a dynamic event that we see in these patients of the clones sort of waxing and waning in terms of their proportion of the overall population of marked cells.
We saw the HMGA2 clone rise to prominence and then it's now waned and we've seen this with others as well.
And it is also important to note that in this early patient treated eight years ago with a first generation vector, the degree of marking - the sort of degree of polyclonality is much lower than we are seeing with the BB305 vector where we are literally seeing thousands of unique integrations. In this patient we were seeing around 100 or so.
And so, any individual marked cell by definition is going to represent a larger proportion of the overall population given the more limited polyclonality. So, our sense is that this is just the natural biology of stem cells playing out and does not represent a clinical concern..
Got it.
And if I can just ask one more question on poly 2, I know that's probably less relevant for that new vector, but can you tell us exactly what effect this integration has had on poly 2 expression? Is it up-regulating expression? Is it placed in your transcript or something else? And if I could sneak in one more question about HGB-206, I know that you are still enrolling, but is there a certain patient treatment you are aiming for? So how many of those patients will be made beta/beta F versus beta/beta-0? And how many will be transfusion dependent versus independent at baseline? Thanks..
So, to your first question, we really can't address that. We are not specifically assessing the effect on the gene integration on protein production. And there is no reason to do so because we are not seeing any clinical events as a consequence of it.
In terms of your other question, you asked about the specific inclusion criteria and the proportion of patients. We are open to enrolling all of those that you described, transfusion dependent, transfusion independent, FS genotype versus S0, but we haven't predefined an explicit proportion..
Got it. Thanks, guys..
Alright. Thank you for the good questions..
Our next question or comment comes from the line of Gena Wang with Jefferies. Your line is now open..
Thank you for talking my questions. I missed the beginning of the call, so I apologize if my questions have already been addressed.
I know you cannot comment much on the details beyond abstract but will we see data from more patients at ASH? And also what level of details will you present at ASH? And my second question is about sickle cell disease and just wanted to understand the thoughts behind increasing number of enrollment for 206..
This is Nick, I think we can clarify. We will be presenting whatever patients we have at this point. So remember the abstract cutoff. And so, for 204 we will be presenting the patients that are there as well as in 205.
In 206, obviously there was more of a placeholder abstract, so there we can't comment on the specific number of patients, but there will be certainly a presentation. So, that also probably doesn't help you a whole lot other than there is certainly going to be more detail.
As far as what kind of detail, we are going to do as we have always done which is outlining a number of the dimensions as we track these patients. So I think there will be sufficient amount of detail for us to assess a lot of the questions that have been asked here.
And I apologize, your second question?.
Yes, the second question, Gena, you asked about why exclusively were we expanding 206. And really the reason is additional patients will provide more data and give us additional options in terms of discussions with the regulatory authorities and then give us more insight into the risk-benefit of LentiGlobin in sickle cell disease.
And so, given the way the program is tracking, it seems like a good modification of the program right now..
Thank you..
Thank you..
Our next question or comment comes from the line of Jeff Chen with Cowen and Company. Your line is now open..
Hi, Jeff, how are you? Apparently not doing that well..
On mute maybe..
We can barely hear you, Jeff..
Is this better?.
Yes. We can actually hear you..
Okay, sorry about that. So thanks for taking my questions. Two if I may. One is on the HGB-206 patient expansion. I know that you said this is initiated by blue.
But what does it mean in terms of gaining regulatory flexibility? Can you give us some of the possible avenues here?.
Good question but no. I think this is - don't over read it here. I think the whole point is we just - more patients, obviously as you get more data as you think about flexibility it is as simple as that.
If you look back at the thal program there, there is also a number of patients that we have there provided some flexibility in what we thought the regulatory path is there and sickle cell is not too dissimilar from that. So, we are just proactively saying we want more patients earlier to assess what to do in the plan.
And then it allows for a broader, more sort of data rich discussion with the agencies..
Got it, got it, okay.
And in terms of the beta-0/beta-0 genotype, I know that we will get more data and more clarity at ASH, but is there any pre-clinical data or otherwise - other data sets that can suggest that - is there any reason why we shouldn't think that VCN should continue to ramp and the transgene 87Q should continue to ramp in the patients?.
I think conceptually speaking we are not viewing the beta-0/beta-0 patients versus the non-beta-0/beta-0 patients different in that regard. We may discover that over time. But I think we have to get into the details of that and watch more patients play out over time.
But I don't think - there is no specific data that you are referencing that would define these patients differently..
Excellent, thanks very much..
Thank you..
(Operator Instructions) And we have a follow-up question or comment comes from the line of Debjit Chattopadhyay with ROTH Capital. Your line is now open..
From a payer perspective, Nick, just to get to the pay for performance, so how do you --?.
Sorry, sorry, sorry, I didn't how you started, from a payer perspective you said?.
Yes. So, from a reimbursement perspective, assuming this goes to market. So, you suggested the pay-for-performance.
Now how do you establish the relative value of transfusion independence versus the reduction in transfusion when you look at the two subtypes? I mean how do you think the payer should look at it?.
Yes, so that is a fair question. I think when I suggested pay-for-performance I don't think I specifically commented on our strategy here. I think as a concept it is a very interesting concept for pricing reimbursement, a shared-risk model, et cetera.
It all comes down to the value, and I think that is where you are going, is the value of the contribution to the patient, to the system, payers, etc., has to be considered. So, as we think about the value of independence versus transduction that is certainly something we have to think about in the context of the system.
But it is very premature to do that and we still need to understand more about the patients and where that actually levels off, et cetera, et cetera. So, I don't think - I think it is premature to comment on that. But it will come down to in all cases ALD, thal, sickle, and oncology to the value that we can bring to the patients in a sustained way..
Great, thank you..
And at this time I'm showing no further questions. So with that I would like to turn the call back over to management for closing remarks..
Thank you and thank you, everyone, for joining us today. We hope to see many of you over the next several weeks at the Credit Suisse conference and the Piper Jaffray conference and of course we hope to see all of you at our investor event at ASH next month. Thank you..
Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect..