Editas Medicine, Inc. (NASDAQ:EDIT) EDIT-301 Clinical Update Call December 6, 2022 8:00 AM ET
Company Participants
Ron Moldaver – Investor Relations
Gilmore O’Neill – President and Chief Executive Officer
Baisong Mei – Senior Vice President and Chief Medical Officer
Mark Shearman – Chief Scientific Officer
Conference Call Participants
Phil Nadeau – Cowen Securities
Gena Wang – Barclays
Matthew Harrison – Morgan Stanley
Joon Lee – Truist Securities
Joel Beatty – Baird
Greg Harrison – BofA
Yanan Zhu – Wells Fargo
Steven Seedhouse – Raymond James
Dae Gon Ha – Stifel
Mani Foroohar – SVB
Ron Moldaver
Good morning, everyone, and thank you for joining the EDIT-301 Clinical Update Webinar. This webinar is being recorded and can be accessed in the future through the same link or through the Investors section of the company’s website. After the webinar, the call will be open to Q&A. [Operator Instructions]
As a reminder, various remarks that we make during this presentation about the company’s future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent Annual Report on Form 10-K, which is on file with the SEC, as updated by our subsequent filings.
In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements even if our views change. This webinar will be presented by Editas Medicine’s CEO, Gilmore O’Neill; and our Chief Medical Officer, Baisong Mei.
Now, I will turn the call over to Gilmore for opening comments.
Gilmore O’Neill
Thanks, Ron. Good morning to you all and thank you for joining us for this webinar presentation of our early clinical experience with EDIT-301. We have shared before that we would want to see fetal hemoglobin levels in excess of 30% so that it may eliminate sickle cell disease symptoms, and that we would want to see a safety profile that is consistent with myeloablative busulfan conditioning and autologous hematopoietic or CD34+ stem cell transplant.
Before I hand over to Baisong Mei, to take you through the data, here are the key takeaways. The initial safety profile of EDIT-301 is consistent with myeloablative busulfan conditioning and autologous hematopoietic stem cell transplant. Both dose participants showed successful engraftment and have stopped red blood cell transfusions, and have not had any vaso-occlusive events or VOEs since EDIT-301 treatment with five months and one month follow-up respectively.
The first patient at five months after EDIT-301 treatment in the RUBY sickle cell disease study had a fetal hemoglobin or HBF of 45.4% and a total hemoglobin of 16.4 g/dL, [high pancellular with] [ph] 96% F cells and a mean corpuscular fetal hemoglobin of 13.8 pg/cell. These preliminary data suggest clinical proof of concept and that Editas medicine has a potential product that can give robust clinical benefit to patients with severe sickle cell disease and has the potential for clinical differentiation in the long-term.
Baisong will now take you through the RUBY study and share the data that support these conclusions.
Baisong Mei
Thanks, Gilmore. Taking a step back, sickle cell disease is an inherited life threatening hematological disorder, manifesting shortly [after birth] [ph]. It can result in severe anemia, unpredictable, and severe attacks of acute pain, mighty organ damages and shorten lifespan. The disorder affects millions of people worldwide, including approximately 100,000 people in the United States.
Sickle cell disease is caused by sickle mutation in better subunit of hemoglobin, a protein contained in red blood cells. Hemoglobin enables red blood cells to carry oxygen to the cells in our body. Normal red blood cells maintain a disk shape. In patients with sickle cell disease, after releasing of oxygen, the sickle hemoglobin polymerized and the red blood cells adopts a sickle cell, impacting the ability of red blood cells to flow smoothly throughout the body and potentially leading to the blockage in small blood vessels.
Sickle cell disease impacts the effectiveness on the longevity of red blood cells. While normal red blood cell has a lifespan of approximately 120 days, sickle cells die within 10 to 20 days, resulting in a shortage of red blood cells in the body and a lower total hemoglobin, a condition called anemia. Sickle cell disease is characterized by painful recurrence of vessel occlusive events and anemia, which result in fatigue among other symptoms and hemolysis, which is a breakdown of red blood cells.
Over time, vessel occlusive events, anemia, and hemolysis all result in heart and lungs working harder than in normal people. The condition also result in an organ damage in nearly all organ systems. Allogeneic bone marrow transplantation can cure sickle cell disease, with less than 20% patient can find massive donors. And there is a risk of [indiscernible] reaction, a very serious complication of transplantation with stem cell from another donor.
Other approved treatments show the limited effectiveness and do not address the underlying cause of sickle cell disease nor do they fully ameliorate disease manifestation. We believe that increased fetal hemoglobin expression will ameliorate the symptoms and complications of sickle cell disease. In fact, natural genetic variants in the [gamma globin] [ph] promoter can cause hereditary persistence of fetal hemoglobin with high levels of fetal hemoglobin in the red blood cells.
In sickle cell disease patient who co-inherit the hereditary persistence of fetal hemoglobin, the patient can have reduction or absence of sickle cell disease symptoms. In fact, there is a negative correlation between the mobility score and the percentage of fetal hemoglobin in peripheral blood of sickle cell disease patient.
In sickle cell disease patient who co-inherit the hereditary persistence of fetal hemoglobin, levels greater than 30% fetal hemoglobin are associated with the significant reduction or absence of sickle cell disease symptom, particularly vessel occlusive events. In addition, the amount of fetal hemoglobin within individual red blood cell is important. That is called corpuscular fetal hemoglobin levels.
When corpuscular fetal hemoglobin level exists 10 pg/cell it is considered clinically meaningful because it prevents red blood cell from [indiscernible]. EDIT-301 employs a unique gene editing approach for high fetal hemoglobin expression. It uses a novel, highly efficient, high fatality CRISPR Nuclease called AsCas12a for gene editing, and targets the promoter region of gamma globin gene 1 and 2 to increase expression of fetal hemoglobin, in order to mimic the natural mechanism of hereditary persistence of fetal hemoglobin. Therefore, treating sickle cell disease.
The RUBY study is a Phase 1/2 study, which has been designed to evaluate the safety, tolerability, and efficacy of EDIT-301 treatment for severe sickle cell disease. The RUBY study will recruit up to 40 patients between the age of 18 and 50 years old who suffer from severe sickle cell disease and has a history of at least two vessel occlusive events per year for the two years prior to enrollment.
The key clinical assessment includes safety events, engraftment, total hemoglobin, fetal hemoglobin, and a vessel occlusive event after EDIT-301 treatment. The first dose of a participant is a 25-year old male, homozygous for sickle mutation, and has suffered a total of eight vessel occlusive events in the two years prior to entering the RUBY study.
The second dose of participant is a 31 year old female, homozygous for sickle mutation and has suffered a total of 6 vaso-occlusive events in the two years prior to entering the RUBY study. EDIT-301 was well tolerated by the two patient dosed. To date, the safety profile has been consistent with that of myeloablative busulfan conditioning and autologous hematopoietic stem cell transplant.
No SAE were reported after EDIT-301 infusion. No AE related to EDIT-301 treatment have been observed. The first patient experienced successful neutrophil engraftment on day 23 and platelet engraftment on day 19. This participant has had five months fall-out period after EDIT-301 dosing.
The second patient experienced successful neutrophil engraftment on day 29 and platelet engraftment on day 37. These participants has had 1.5 months follow-up period after EDIT-301 dosing. No vessel occlusive events would reported in these two patient following dosing. This figure shows the total hemoglobin level over time in patient one after EDIT-301 dosing, as well as the percentage of hemoglobin fractionation.
The X axis represented the follow-up period after infusion of EDIT-301. The Y axis represent the total hemoglobin level and the total hemoglobin level values are denoted on top of the bars. The reference range for normal hemoglobin of the central lab is 13.6 to 18 g/dl for men. Hemoglobin fractions are color coded in each bar with the fetal hemoglobin represented at the bottom of the bar in orange.
We are pleased to see that these first patient’s total hemoglobin increased from 11.9 g/dl at baseline into the normal range with the 16.4 g/dl [and] [ph] five months after infusion of EDIT-301. This represents an increase of more than 4 g/dl of hemoglobin.
In addition, the first patient, the fetal hemoglobin fraction increased from 5% of baseline to 45.4% at 5-months after [his infusion] [ph]. As a reminder, sickle cell disease patient with 30% fetal hemoglobin may have no sickle cell symptom. For maximize the clinical benefit of treatment, fetal hemoglobin expression needs to be shared across red blood cells to ensure that the tendency to sickle is eliminated from as many red blood cells as possible. And indeed, five months after treatment, 96% of the first patient’s red blood cells express fetal hemoglobin that is they are F-cells as represented by blue bar in the left panel.
As I indicated earlier, fetal hemoglobin level in excess of 10 pg/red blood cell are considered clinically meaningful because those level will prevent that red blood cell from sickling. These patients mean corpuscular fetal hemoglobin level are represented by gray bars in the right hand panel, reaching 13.8 pg/red blood cell after five months of follow-up.
In summary, EDIT-301 was well tolerated by the first two participant dosed, no SAE occurred after EDIT-301 treatment, no AE was reported as related to EDIT-301. Both dosed participant should successful engraftment had no vaso-occlusive event since EDIT-301 dosing with five months and 1.5 months follow-up period respectively.
For efficacy, the first patient dosed showed a robust response to EDIT-301 treatment. At month five after EDIT-301 infusion, his total fetal hemoglobin was well in the normal range, at 16.4 g/dl. His fetal hemoglobin reached 45.4% and 96% of red blood cells with F-cells. Mean corpuscular fetal hemoglobin level reached 13.8 pg/red blood cells, where about the clinical meaningful threshold of 10 pg/cell. These initial preliminary data suggested clinical proof of concept. We look forward to share more data from this study expected in the middle of next year.
Now, I will turn the call back to our CEO, Gilmore.
Gilmore O’Neill
Thanks, Baisong. These encouraging preliminary data suggest clinical proof of concept and that Editas Medicine has a potential product that can give robust clinical benefit to patients with severe sickle cell disease and has the potential for clinical differentiation in the long-term. We expect to provide more data from these first two patients and additional patients in the middle of 2023.
I have previously shared that since my arrival at Editas, we are implementing the use of new therapeutic target selection criteria that use translational, clinical, and commercial factors to maximize the probabilities of technical, regulatory, and commercial success of our pipeline. EDIT-301 fits well within these parameters.
Clinical execution is a top priority for us, and we will continue to drive forward on this. We look forward to sharing more details around the criteria and our strategic plans in the coming months. For now, we thank all patients, their families, investigators, study site staff members, our CRO partners, and our employees.
And I will now turn the call to Ron to start our Q&A session. Ron?
Question-and-Answer Session
A – Ron Moldaver
Thank you, Gilmore. [Operator Instructions] Our first question comes from Phil Nadeau at Cowen Securities. Phil? You will be asked upon mute. You may then ask your question.
Phil Nadeau
Good morning. Thanks for taking our questions. Just two from us. First on the data, it looked like the mean corpuscular fetal hemoglobin had a big increase between months at four and five, any sense as to why you’d have a big increase that far after dosing? And then second, on the mid-2023 data, any sense of how many patients you’re likely to have at that time point? Thank you.
Gilmore O’Neill
So, Phil, what I might do is start with the second question and then I’ll ask Baisong to talk about the first part of your question. Currently, we’re not prepared to share specific numbers for the number of patients that we will be enrolling and dosing in 2023. We do anticipate having a larger number of patients mid-year. But I think the key point to note is that we have already enrolled freezed cells from and edited cells from additional patients and are currently reviewing per protocol the first two sentinel patients data with our Independent Data Monitoring Committee. And once we’ve completed that review, we’ll be scheduling those patients for dosing in the very near future.
We are very happy with current sites and the work that they have done on screening and enrolling patients where actively adding new additional sites. And we will expect and in fact anticipate an increase in excitement amongst investigators, patients, and patient organization with the sharing of today’s data.
With regard to the first question that you posed, I’ll just pass that to Baisong.
Baisong Mei
Yes. Thanks for your question. It’s Baisong. Yeah. So, the mean corpuscular fetal hemoglobin level is determined by several factors at when is that to be total amount fetal hemoglobin and then the number of red blood cells. And you can see for the total fetal hemoglobin increases from be month four to month five. And then you can also see the increase of mean corpuscular increase of the – in the next slide. And they may or may not be exactly linear between these two parameters because they are red blood cells, other assay variations on that too, but you can see the trend matches between those two numbers.
Phil Nadeau
Yeah. That’s very helpful.
Gilmore O’Neill
I’d say the key point – sorry, Phil, the key takeaway obviously is that we are exceeding that 10 pg/cell threshold, which we believe is meaningful to prevention of sickling in those cells.
Phil Nadeau
That’s very helpful. Congrats on the data and thanks for taking our questions.
Ron Moldaver
Thanks, Phil. Our next question comes from Gena Wang at Barclays. Gena, you may go ahead.
Gena Wang
Thank you for taking my questions. I also wanted to add my congrats on a very impressive data. So, I wanted to ask, since your patient, you know, like, seems like the data so far, you know, pretty impressive, are you planning to go after more severe patients like beta zero patient? And also, again, I’m pretty sure you got this question a lot. You know, giving that now, both bluebird or CRISPR likely, hopefully, you know, may get a drug approval sometime later in 2023. How do you see the differentiation based on your clinical profile?
Gilmore O’Neill
Thanks very much, Gena. Just to recapitulate your question, I think two questions. One about the differentiation. And I think the second was about the criteria or our life cycling ambition for the program. Let me address the first – the second part, and then I’ll pass it to Baisong to discuss the protocol and are clinical development plans. So, obviously, we’re very encouraged, as you say, by these preliminary data for our single patient.
I think a critical element is that we have a very unique therapeutic strategy in that we’re using our own engineered high fidelity, high efficiency AsCas12a and we’re targeting the gamma globin promoter. The combination of those two approaches, we believe created a potential for differentiation, which we expect or hope to see over the execution of our clinical program.
And I think the key point is that by using a high efficiency, high fidelity method with a significant reduction in off-target editing, as well as by targeting the gamma globin promoter where stress releases is not required to drive a fetal hemoglobin expression. And indeed, in our hands, the choice of that gamma globin promoter as a target increases or maximizes long-term erythroid health.
We believe those are all factors that ultimately could result in significant differentiation, both with robustness and potential durability of the fact, which would be important in controlling not just faster [occlusive events] [ph], but very importantly, the other significant complications of this incredibly serious disease. And I think it’s worth pausing for a moment and remembering that this is actually a pediatric disease, which requires substantial support of care to actually support children and allow them to survive into adolescence and adulthood. Baisong?
Baisong Mei
Yeah. Thanks, Gena, for your question. Yes, we are including a [beta zero patient] [ph]. So, we are – it’s for the genotype perspective, we’re including homozygous patient who have mutation on both earlier as we – the two patient we presented and we’re including the heterozygous [data zero] [ph] as well as data positive heterozygous patient. And we are – when we get more data, we’re intending to actually go into a protocol, allow or go into further expand the genome type of patient.
And towards the severity, as we mentioned that I just mentioned earlier, we are targeting severe patients and then those two patients presented; one had eight occlusive events in the past two years, and the other patient had six occlusive events in the past two years before enrolling the study.
Gilmore O’Neill
One other thing I’d just like to finish off is by making the point that beyond differentiation, we believe this potential product is competitive. And based on our own personal experience, in previous lives, as well as a more general experience over the last few years around the launch of complex therapeutics, we expect and strongly believe that the vast majority of the prevalent population will be awaiting treatment at the time of our launch.
Gena Wang
Thank you very much.
Ron Moldaver
Our next question comes from Madhu Kumar at Goldman Sachs. Madhu, you may proceed with your question.
Unidentified Analyst
Hey guys, thanks for taking our question. This is Rob on for Madhu. I guess my first question is, from your interactions with regulators, what would be a sufficiently sized patient data set and follow-up to consider a BLA? And then also, how are you thinking about any strategies to obviate the use of busulfan as a preconditioner?
Gilmore O’Neill
Thanks very much. I will make some brief remarks and then Baisong can actually expand somewhat on them. With regard to the number of patients that are required I think the key is that the data that we are generating in this current protocol, all of those are usable in a marketing application. With regard to our negotiations and interaction with the regulators, that would be something that’s ongoing over the coming year or so and we’ll have much greater clarity and be able to comment about that when we have clarity on the numbers and the duration of follow-up.
And then with regard to – sorry, the second question.
Baisong Mei
Busulfan.
Gilmore O’Neill
Busulfan. Yes, we are obviously interested in looking beyond busulfan and milder conditioning therapies as it is a – it’s an important burden for patients and treatment sites across the stem cell transplant space. So, we are actually interested in that and pursuing that. Baisong, anything to add?
Baisong Mei
Yes. Yes. Just to add on that, absolutely, as Gilmore mentioned, we are actively looking to monitor the space of the alternative conditioning regimens. And what I want to add is that the for sickle cell patients, they are really a severe disease and their bone marrow health is [indiscernible] inflammation and other conditions is a very difficult group patient to get engraftment. So, an appropriate and sufficient condition is important for this patient population.
Unidentified Analyst
Thanks.
Ron Moldaver
Our next question comes from Matthew Harrison at Morgan Stanley. Matt, you may now go ahead.
Matthew Harrison
Great. Can you hear me okay?
Gilmore O’Neill
Yes.
Matthew Harrison
Thanks for taking the question. I guess two for me. One, just can you comment, obviously, — it will take some – it potentially will take some time to see the clinical differentiation you’re talking about. What would you be monitoring in the near-term or mid-term to see that potential differentiation of space, especially as you gain a greater number of patients? And then secondly, can you just comment on some of the other blood marker parameters like, [ritic’s] [ph], LDH and bilirubin?
Gilmore O’Neill
Yes. So, I will – let me just start and then I’ll pass the question on other parameters to our Chief Medical Officer, Baisong. With regard to the follow-up and the parameters we’re looking for, we’ll be looking across multiple parameters on the clinical trials. When we look to potential for differentiation, we are looking to both safety with a different potential for off-target editing.
And in addition, on the efficacy side to potentially more robust responses and durability and that robustness and durability, we can – has an impact potentially on the symptoms, not just of VOEs, but indeed on cardiopulmonary function, other end organ health, as well as exercise tolerance and measures of quality of life.
With regard to other blood markers, we are following those in the clinical protocol and we’ll be sharing those when we have longer follow-up data and more patients.
Matthew Harrison
Thank you.
Ron Moldaver
Our next question comes from Joon Lee at Truist Securities. Joon, you may now unmute and ask your question.
Joon Lee
Thanks. Congrats on the data and thanks for taking the questions. What proportion of the cells that you edited had [biallelic edits] [ph] and were you selecting for those we transplant? And what were the doses of the cells infused into these two patients? Thank you.
Gilmore O’Neill
Sorry, Joon, I heard the first part of your question about biallelic edit, but I missed the second part of your question.
Joon Lee
Yes. So, number one, yes, so what proportion of the cells you manipulated had the biallelic edits? And were you selecting for the cells with biallelic edits when you transplanted the patients? And what were the cells at the doses of the cells used in these two patients? Thank you.
Gilmore O’Neill
Okay. Thanks very much, Joon. What I’m going to do is have Mark Shearman, our Chief Scientific Officer, who joins us address the editing question, and then Baisong will talk about dose.
Mark Shearman
Yes. Hi, Joon, So, short answer is that the majority of cells have biallelic edits, as you would have seen from the data were and what we’ve published preclinically, we’re getting in excess of 80% [indiscernible] formation in the starting material and [indiscernible] transplantation studies that stayed like that out to five months for the duration of that study. And then dose-wise, Baisong, you might want to comment on that?
Baisong Mei
Yes. Thanks, Joon. So, we are having the minimum dose of [3 million cells per kilo] [ph], and certainly, we were better to different patients will have a different dose based on the cell collection on that too, but that’s kind of those we are aiming for.
Joon Lee
So, just a quick follow-up. Would you say that the two patients that you dose were in the lower side of the dose that you’re attempting or…?
Gilmore O’Neill
Yes. Okay. Sorry, I missed your question. Joon, yes. So, the for the first patient the dose was [10 million cells per kilo] [ph] and the second patient with 4 million [cells per kilo] [ph].
Joon Lee
Got it. And should we think about that as the, sort of the normal range going forward or would you attempt higher dose or lower dose?
Baisong Mei
No. I think for all these autologous transplantation, they are with a range of dose and that – there’s no specific data such as in dose response per se, but there is a requirement of minimum dose for the general practice.
Joon Lee
Got it. Thank you.
Ron Moldaver
Thank you. Our next question comes from Joel Beatty at Baird. Joel, you may now go ahead.
Joel Beatty
Thanks. So, with the positive data today, does this impact your plans to accelerate development of any of your other agents in your pipeline or partnering discussions?
Gilmore O’Neill
Thanks very much, Joel. From a strategic point of view, I think, I earlier stated that since I got here in the middle of the year, I’ve been working very closely with Baisong, Mark, and other members of the executive team as we evaluate and refocus our portfolio strategy and pipeline and looking forward to sharing that in the coming months.
Nevertheless, I can say that we are certainly focusing on advancing our 301 program. I already talked about the fact that we’ve already collected and edited cells from patients that we have sites – multiple sites activation or activating more sites, but we’re not doing that at the expense of our focus on our pipeline, but I look forward to sharing more details of that in the coming months.
Joel Beatty
Great. Thank you.
Ron Moldaver
Thank you. Our next question comes from Greg Harrison at BofA. Greg, you may now unmute and ask your question. Greg, if you are there, please unmute to proceed.
Greg Harrison
Hi. Can you guys hear me?
Ron Moldaver
Yes.
Greg Harrison
Hey, thanks for taking the question. Obviously, it’s hard to tell for one patient, but do you have any thoughts on how patient one achieved a relatively high total hemoglobin level even with the fetal hemoglobin fraction more in-line with what we’ve seen in other gene-edited sickle cell patients?
Gilmore O’Neill
I think – thanks very much, Greg. I think that this is – thank you for your question. I think more importantly, one of the things we want to be very careful about is speculating based on one patient and overinterpreting those data. I think the key thing I want to say is, we are really encouraged by this data set from a single patient. We think that it gives very robust proof of concept.
And we’re also very happy to see these results with our unique therapeutic targeting strategy using AsCas12a, and targeting of the gamma globin promoter. I think beyond that, we want to be very careful and prudent, and we look forward to actually sharing more data next year, and I think when we can actually speak with more confidence about everything that we’re seeing.
Greg Harrison
Got it. Fair enough. And do you have any sense of what we should expect in that mid-year update as far as the thalassemia program? Will there be an update there or would it be just sickle cell?
Gilmore O’Neill
We are hoping to give a comprehensive review across the data sets from this program in the middle of next year.
Greg Harrison
Great. Thanks for taking the questions.
Ron Moldaver
Thank you. Our next question comes from Yanan Zhu at Wells Fargo. Yanan, you may now unmute and ask your question.
Yanan Zhu
Great. Thanks for taking the questions and congrats on the data. What are the rates of [allele editing] [ph] [ph] in the drug products for patient one and patient two? Have you performed bone marrow or peripheral blood analysis for [allele editing] [ph] [ph] rates? And then any color on patient number two’s hemoglobin levels at the 1.5 month follow-up? How does that patient’s fetal hemoglobin as a percentage of total hemoglobin compare with the data from patient one at a similar time point? Thank you.
Gilmore O’Neill
Thanks very much, Yanan. I’ve shared the answers with Mark on the first question and based on for the lateral questions, but at a high level, we’ve actually seen very good [allele editing] [ph] across the patients that we have edited and bone marrow is a part of the protocol these patients will – and those are set at future time points. And then I think the final thing I can say with patient two’s data is that we are encouraged by the results we’ve seen to date.
We haven’t shared the specifics of those numbers because, as we have said, we believe that the timing for truly recognizing the actual [quantitation hemoglobin] [ph] levels is best set around that four to six month period where historically we are seeing plateauing, and also where you’ve actually washed out the effects of the red cell transplantations that many patients require to stabilize them and support them prior to and support them during the rigors of the transplant procedure. But maybe, Mark, do you want to comment on the specifics of the editing?
Mark Shearman
I think what we have mentioned in the past, we’ve exceeded 80% editing across a number of different cell populations, both normal sickle cell and TDT and based on the preclinical data, our expectation is that editing rate will continue, both in peripheral blood and bone marrow at later time points when we have acquired that data.
Baisong Mei
Yes. Yes. Thanks for your question. And I’ll just add on the editing point, right, from a clinical perspective. We also see that the high editing in the editing of CD34 cells in the clinical manufacturer, as well as for the peripheral [indiscernible] cells from the first patient, and we – as Gilmore mentioned, we are certainly scheduled also to have bone marrow, but bone marrow will have a less frequent sampling as you would imagine. So, we are very pleased with the editing data.
And then regarding the second patient and because there are reasons, as Gilmore mentioned, that one is that the [hemotological parameter] [ph] were plateau. And secondly, it could be the very beginning of the data after the transfusion can be confounded by the red blood cell transfusion, but we are very, very encouraged with the data we’ve seen so far. We look forward to share with you and all about this patient, as well as subsequent patients.
Yanan Zhu
Great. Thanks for all the color. Congrats again.
Ron Moldaver
Thank you. Our next question comes from Steven Seedhouse of Raymond James. Steve, you may now unmute and ask your question.
Steven Seedhouse
Yeah, hi, thank you. I was hoping you could comment on just the doses of the conditioning regimen and how that compares to some of the other HSCT genetic medicine programs? And then also TPO post-transplant, is this standard? And lastly, I just wanted to confirm if these were the first two patients that were at [indiscernible] or if anyone who’s been [indiscernible] but ultimately not transplanted with EDIT itself? Thanks.1
Gilmore O’Neill
So, I certainly, I’ll probably come back and ask you to repeat the second question. With regard to the conditioning dose paradigm, we’re using a kinetic or pharmacokinetically controlled dosing protocol, which is very standard and common across stem cell transplantation. With regard to your last question on editing, we have actually edited. We have collected and edited additional patients over the two that we have actually dosed. And we’re not actually sharing, you know significant details on those data until we’ve actually dosed more patients where we can actually make reasonable inferences and correlations.
Could you repeat your second question? I couldn’t hear it.
Steven Seedhouse
Yes. Apologies for that. It was just on the thrombopoietin use comment in graph on Slide 10. And just if this is standard and these types of studies are something unique to your protocol?
Gilmore O’Neill
Thanks. I didn’t actually hear the word again, you said a word I can’t hear it.
Steven Seedhouse
It’s a comment on Slide 10, just the three consecutive measures of platelet count starting at least 7 days after last platelet transfusion and 10 days after TPO, I’m just curious if that TPO feature…?
Gilmore O’Neill
Yes, I see. I just couldn’t hear what you were saying [indiscernible]. Sorry, yes. This is just a definition in the protocol. And so because when you have a platelet transfusion, you are kind of confounding the accounting of that, right. So, that’s kind of what the condition. And then TPO in case the TPO is needed, they’re also been part of that. So, for these patients, that is three cell – platelet count and then [meet the criteria] [ph] and the day 37 being considered to be – or [19] [ph] being considered [palliative engraftment] [ph]. And this is a very standard, again, this is a very standard approach for monitoring and calling platelet engraftment for stem cell transplantation.
Steven Seedhouse
Got it. That was my question. Thank you so much.
Ron Moldaver
Thank you. Our next question comes from Dae Gon Ha at Stifel. Dae Gon, you may now unmute and ask your question.
Dae Gon Ha
Hey, great. Good morning. Thanks for taking our questions and let me add my congrats on the first patient data. I wanted to go back on the differentiation aspect. I forgot the slide number, but you were showing a natural history-ish showing the correlation between HbF and the occurrence of the various [VOEs] [ph]. I think it ended on the x-axis about 25%. So, I was just wondering at what point on the HbF do you end up getting an ablation of all the VOEs that were characterized in that paper, if you have that? And then secondly, on the point of differentiation, I think that’s the main focus that a lot of people have been triangulating here. Since you’re measuring a lot of different parameters and data, I guess I’ll ask it a different way, what duration of follow-up do you think would start manifesting the key differentiation, whether it’s VOEs or end organ damage, compared to some of the other therapies that are in development today? Thanks very much.
Gilmore O’Neill
Thanks very much, Dae Gon. With regard to the graph, I think it was actually on Slide 6. That is a graph that we used is rather nicely laid out. It’s from a review from Steinberg at [indiscernible], but if you look at the data [at sites] [ph] and the published – additional published data, this is where we kind of set the 30% threshold and the experience based on the natural variants that drives hereditary persistence of fetal hemoglobin, where that actually is coinherited with the risk of sickle cell disease, sort of that natural experiment, if you will, has demonstrated a substantial reduction, if not elimination of the risk for VOEs.
With regard to differentiation, the duration of follow-up to see impact on, for example, robustness of the effects, as well as the [durability effect] [ph] will actually be a matter of empiric observation. And I think that is something that we will be able to talk about with more confidence as we extend our experience with human follow-up. And the same will be true around the impact of durability on vaso-occlusive events.
Dae Gon Ha
Great. Thanks so much.
Ron Moldaver
Thank you. Our next question comes from Mani Foroohar at SVB. Mani, you may now go ahead.
Mani Foroohar
Hey, guys. Thanks for taking the question. Obviously, a lot of the nuances are on the data, you’ve already answered. I like to follow up on Gena’s question, as also has been touched by a few others around clinical differentiation, obviously, with only two patients, the data looks like clean this early, but it’s hard to compare to larger data sets at this point. Looking forward, what would you need to see as you get to larger data sets, et cetera, to give yourself greater confidence and conviction in clinical differentiation versus, for example, bluebird, for example, CRISPR/Vertex, are the key metrics you’re looking at hemoglobin levels, VOEs, metrics of end organ microvascular damage. Like what are the – like what would you guys be looking for over the next 6, 12, 18, 24 months? And why should our attention be focused as proof points for clinical differentiation?
Gilmore O’Neill
Thanks very much, Mani. I think there are a couple of things that I’d like to say. The first is, notwithstanding differentiation before we get there, that we believe that this potential product is actually competitive as is that there is space in the sickle cell treatment space for more than one product. And I think that’s a very important thing to remember. Indeed also a strong belief based on our own personal experiences in previous lives, as well as the general experience with complex therapeutics and the fact that the vast majority of the prevalent population will still be untreated when we launch.
With regard to the specifics of differentiation, I think you’ve touched on some of the parameters that we’re looking for. But I think it’s very important, as we have stated to remember that this is an extraordinary serious disease, which actually has multiple impacts across multi-organs and the actual pathogenetic mechanisms are actually rather complex, driven both the combination of anemia, sickling, and hemolysis.
And so, as a result, we’ll be looking across a number of both hematologic parameters, parameters of hemolysis, as I said earlier, as well as clinical measures of end organ damage across multiple organ systems. And I think it will be the totality of the data that will actually help us determine differentiation over the coming years. And indeed, we actually suspect that, that differentiation could actually extend beyond the 24-month period and into longer, sort of medium-to-longer-term follow-up.
Mani Foroohar
That’s helpful. If I can follow up, I guess, the inverse of that question, which is presuming that when you achieve commercialization, there is a large proportion of the prevalent population untreated. That sounds like a fair assumption to me. Based upon your interactions thus far with your principal investigators, other clinicians, patient communities, et cetera, what are the key metrics you believe they will be looking for as they choose in this hypothetical world between multiple approved therapies, which have a functionally curative intent, such as this one that you’re developing?
Gilmore O’Neill
Thanks very much. I’m actually going to share that question with Baisong in a second. But I think the key thing that certainly in my experience of therapeutic development and approvals is that the empiric data as they evolve have an enormous impact on how investigators PIs and experts think about the therapeutics and the parameters in which they’re interested in making their clinical decisions and similarly for the patients. But Baisong, based on your [indiscernible], you may want to share your insights?
Baisong Mei
Yes, absolutely. So, I mean, I have – since I joined, I mean in my prior time also, since I joined we love interactions with investigators as well as the [indiscernible] from patient community. So, I can see that the feedback I heard was that there’s [enthusiasm] [ph] for this gene editing program. I mean, when [indiscernible] mentioned that this patient is actually more interested into these autologous gene editing program then allogeneic transplant because allogeneic transplant, as you mentioned, [really] [ph] have some drawbacks on that too, not only just finding [re-matched donors] [ph]. So, that’s kind of one thing.
The other thing is, that for this patient committee, not only investigators, even the patient community, they are very much interested [with science] [ph]. And they also understand actually, we have a different molecule, different approach. So, they are interested in that, too. So, this not only I hear from investigators, but also the patient community. I mean as you probably well know, many rare disease communities [indiscernible] I work a lot of hemophilia, as well as sickle cell, they are very well educated. They are really getting to the science.
Mani Foroohar
Thanks guys. That’s really helpful.
Ron Moldaver
Thank you. This now concludes the Q&A portion of the webinar. Thank you to everybody for joining. You may now disconnect.
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