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 investor section of the company's website. After the webinar, the call will be open to Q&A. To ask a question, please click the Raise Hand feature in the webinar portal. 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 CEO, Gilmore O'Neill, and our Chief Medical Officer, Baisong Mei. Now I will turn the call over to Gilmore for opening comments.
Thanks, Ron. Good morning to you all, thank you for joining us for this web 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 CD 34 positive 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 pan-cellularity with 96% F-cells, and a mean corpuscular fetal hemoglobin of 13.8 pg per 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.
Thanks, Gilmore. Taking a step back, sickle cell disease is an inherited life-threatening hematological disorder manifesting shortly after birth. It can result in severe anemia, unpredictable and severe attacks of acute pain, multi-organ damages, and shortened 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 beta subunit of hemoglobin, a protein contained in blood cells. Hemoglobin enables red blood cells to carry oxygen to the cells in our body. Normal red blood cells maintain a disc shape. In patients with sickle cell disease, after releasing of oxygen, the sickle hemoglobin polymerize and the red blood cells adopts a sickle shape, 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 10-20 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 vaso-occlusive events and anemia, which result in fatigue, among other symptoms, and hemolysis, which is the breakdown of red blood cells. Over time, vaso-occlusive events, anemia, and hemolysis all result in heart and lungs working harder than in normal people. The condition also result in end organ damage in nearly all organ systems.
Allogeneic bone marrow transplantation can cure sickle cell disease, less than 20% patient can find matched donors, and there is a risk of graft versus host 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 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 % 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 a significant reduction or absence of sickle cell disease symptom, particularly vaso-occlusive events. In addition, the amount of fetal hemoglobin within individual red blood cell is important. That is called mean corpuscular fetal hemoglobin levels. When mean corpuscular fetal hemoglobin level exceeds 10 picogram per cell, it is considered clinically meaningful because it prevents that red blood cell from sickling. EDIT-301 employs a unique gene editing approach for high fetal hemoglobin expression.
It uses a novel, highly efficient, high fidelity 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 I/II 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 vaso-occlusive events per year for the two years prior to enrollment. The key clinical assessment includes safety events, engraftment, total hemoglobin, fetal hemoglobin, and vaso-occlusive event after EDIT-301 treatment.
The first dosed participant is a 25-year-old male, homozygous for sickle mutation and has suffered a total of 8 vaso-occlusive events in the two years prior to entering the RUBY study. The second dosed participant is a 31-year-old female, homozygous for C mutation and has suffered a total of six vaso-occlusive events in the two years prior to entering the RUBY study. EDIT-301 was well-tolerated by the two patients 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 5 months follow-up period after EDIT-301 dosing. The second patient experienced successful neutrophil engraftment on day 29 and platelet engraftment on day 37.
This participant has had one and a half months follow-up period after EDIT-301 dosing. No vaso-occlusive events were reported in these two patients following dosing. This figure shows the total hemoglobin level over time in patient one after EDIT-301 dosing, as well as the % of hemoglobin fractionation. The X-axis representing the follow-up period after infusion of EDIT-301. The Y-axis representing 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 bottom of the bar in orange.
We are pleased to see that this first patient's total hemoglobin increased from 11.9 g/dL at baseline into the normal range with a 16.4 g/dL at 5 months after infusion of EDIT-301. This represents an increase of more than 4 g/dL of hemoglobin. The first patient fetal hemoglobin fraction increased from 5% at baseline to 45.4% at 5 months after his infusion. 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.
Five months after treatment, 96% of the first patient's red blood cells expressed fetal hemoglobin, that is, they are F-cells, as represented by the blue bar in the left panel. As I indicated earlier, fetal hemoglobin level in excess of 10 pg per 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 per red blood cell after five months of follow-up. In summary, EDIT-301 was well-tolerated by the first two participants dosed. No SAE occurred after EDIT-301 treatment. No AE was reported as related to EDIT-301.
Both dosed participants showed successful engraftment, had no vaso-occlusive events since EDIT-301 dosing, with five months and one and a half 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 were F-cells. Mean corpuscular fetal hemoglobin level reached 13.8 pg per red blood cells, well above the clinical meaningful threshold of 10 pg per cell. This 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. I will turn the call back to our CEO, Gilmore.
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, 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. I will now turn the call to Ron to start our Q&A session. Ron?
Thank you, Gilmore. As a reminder, to ask a question, please click the Raise Hand button at the bottom of the webinar portal. Our first question comes from Philip Nadeau at TD Cowen. Phil, you will be asked to unmute. You may then ask your question.
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 four and five. Any sense as to why you'd have a big increase that far after dosing? Second, on the mid-2023 data, any sense of how many patients you're likely to have at that time point? Thank you.
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 at mid-year. I think the key point to note is that we have already enrolled freeze cells from and EDIT cells from additional patients and are currently reviewing per protocol the first two sentinel patients' data with our Independent Data Monitoring Committee. 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 our patients. We're 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.
Thanks for your question, this is Baisong. The mean corpuscular fetal hemoglobin level is determined by several factors. One is that the total amount fetal hemoglobin and then the number of red blood cells. You can see for the total fetal hemoglobin, it increases from the month four to month five. You can also see the increase of mean corpuscular in the next slide. There may or may not be exactly linear between these two parameters because there are red blood cells, there are other assay variations and on there too. You can see the trend matches between those two numbers.
That's very helpful.
Can I say the key point. Sorry, Phil. The key takeaway obviously is that we are exceeding that 10 pg per cell threshold, which we believe is meaningful to preventions, prevention of sickling in those cells.
That's very helpful. Congrats on the data, and thanks for taking our questions.
Thanks, Phil.
Our next question comes from Gena Wang at Barclays. Gena, you may go ahead.
Thank you for taking my questions. I also wanted to add my congrats on a very impressive data. 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? Again, I'm pretty sure you got this question a lot. You know, given that now both Bluebird and 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?
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, that second part, and then I'll pass it to Baisong to discuss the protocol and our clinical development plans. 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. 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 erythropoiesis is not required to drive fetal hemoglobin expression. 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 effect, which will be important in controlling not just vaso-occlusive events, but very importantly, the other significant complications of this incredibly serious disease. I think it's worth pausing for a moment and just remembering that this is actually a pediatric disease which requires substantial supportive care to actually support children and allow them to survive into adolescence and adulthood. Baisong.
Yeah. Thanks, Gena, for your question. Yes, we are including beta-zero patients. It's for the genotype perspective. We including homozygous patient who have mutation on both allele as we, the two patient we presented, and we including the heterozygous beta-zero as well, as well as beta-plus homozygous patient. We are, when we get more data, we are intending to actually go into protocol allow or go into further expand the genotype of the patient. Towards the severity, as we mentioned that, I just mentioned earlier, we are targeting severe patients. When these two patients presented, one had 8 occlusive event in past 2 years, and the other patient had six occlusive event in the past two years before enrolling in the study.
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. You know, based on our own personal experience, you know, 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.
Thank you very much.
Thank you. Our next question comes from Madhu Kumar at Goldman Sachs. Madhu, you may proceed with your question.
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?
Follow-up to consider, a BLA. How are you thinking about any strategies to obviate the use of busulfan as a pre-conditioner?
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 will 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. Sorry, the second question.
Busulfan.
Busulfan. Yes. We are obviously interested in looking beyond busulfan and milder conditioning therapies, as it's an important burden for patients and treatment sites across the stem cell transplant space. We are actually interested in that and pursuing that. Baisong, anything to add?
Yeah, yeah, just to add on that, absolutely, as Gilmore mentioned, we are actively looking into and monitor the space of the alternative conditioning regimens. What I wanna add is that for sickle cell patient, they are in a really rare severe disease, and their bone marrow health is a lot of inflammation and other conditions. It's a very difficult group patient to get engraftment. An appropriate and sufficient conditioning is important for this patient population.
Thanks.
Our next question comes from Matthew Harrison at Morgan Stanley. Matt, you may now go ahead.
Great. Can you hear me okay?
Yes.
Okay, great. Thanks for taking the question. I guess, two for me. One, just, can you comment, obviously, you know, it'll take some time to see the clinical differentiation you're talking about. What would you be monitoring in the near term or midterm to see that potential differentiation, especially as you gain a greater number of patients? Secondly, can you just comment on some of the other blood marker parameters like reticulocytes, LDH, and bilirubin?
Yeah. 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. In addition on the efficacy side to potentially more robust responses and durability. That robustness and durability 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.
Thank you.
Thanks. Our next question comes from Joon Lee at Truist Securities. Joon, you may now unmute and ask a question.
Thanks. Congrats on the data, and thanks for taking our questions. You know, what proportion of the cells that you edited had biallelic edits? Were you selecting for those when you transplanted? What were the doses of the cells infused into these two patients? Thank you.
Sorry, Joon Lee, I heard the first part of your question about biallelic edit, and but I missed the second part of your question.
Yeah. Number one, yeah. You know, what proportion of the cells you manipulated had the biallelic edits? Were you selecting for the cells with biallelic edits when you transplanted the patients, what were the cells, the doses of the cells used in these two patients? Thank you.
Okay, thanks very much, Joon. What I'm going to do is have Mark, our chairman, our chief scientific officer who joins us, address the editing question, and then Baisong will talk about dose.
Yeah. Hi, Joon. Short answer is that the majority of cells have biallelic edits, as you would have seen from the data where from what we've published pre-clinically, we're getting in excess of 80% indel formation in the starting material. Certainly in the mouse xenotransplantation studies that stayed like that up to 5 months for the duration of that study. Dose-wise, Baisong, you might wanna comment on that. Yeah. Thanks, Joon. We are having the minimum dose of 3 million cells per kilo, and certainly, we will that to different patient will have different dose based on the cell collection.
On that too, but that's kind of those we are aiming for.
Just a quick follow-up. Would you say that the two patients that you dosed were in the lower side of the dose that you're attempting or?
No.
Yeah.
Okay. Okay. Sorry, I missed your question, Joon. Yes. For the first patient, the dose was 10 million cells per kilo. The second patient was 4 million cell per kilo.
Got it. Should we think about that as the sort of the normal range going forward, or would you attempt higher dose or lower dose?
No, I think for all these autologous transplantation, they're all with a range of dose and that there's no specific data suggesting dose response per se, but there is a requirement of minimum dose for the general practice.
Got it. Thank you.
Thank you. Our next question comes from Joel Beatty at Baird. Joel, you may now go ahead.
Thanks. 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?
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 EDIT-301 program. I already talked about the fact that we've already collected and edited cells from patients that we have sites, multiple sites activated or activating more sites.
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.
Great. Thank you.
Thank you. Our next question comes from Greg Harrison at B of A. Greg, you may now unmute and ask your question. Greg, if you're there, please unmute to proceed.
Hey, can you guys hear me?
Yes.
Hey, thanks for taking the question. Obviously it's hard to tell from one patient, 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?
You know, thanks very much, Greg. I think that, thank you for your question. I think more importantly, one of the things we want to be very careful about is speculating, based on, you know, one patient, and over-interpreting those data. I think the key thing I want to say is we are really encouraged by this data set from that single patient. We think that it gives very robust proof of concept. 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.
Got it. Fair enough. Do you have any, you know, sense of what we should expect in that mid-year update as far as the thalassemia program? Will there be an update there, or will it be just sickle cell?
We are hoping to give a comprehensive review across the data sets from this program in the middle of next year.
Great. Thanks for taking the question.
Thank you, Greg.
Thank you. Our next question comes from Yanan Zhu at Wells Fargo. Yanan, you may now unmute and ask your question.
Great. Thanks for and congrats on the data. What are the rates of allele editing in the drug products for patient one and patient two? Have you performed bone marrow or peripheral blood analyses for allele editing rates? Any color on patient number two's hemoglobin levels at the One and a half month follow-up, how does that patient's fetal hemoglobin as a percentage of total hemoglobin compare with the data from patient one at similar time points? Thank you.
Thanks very much, Yanan. I share the answers with Mark on the first question and Baisong for the latter questions. At a high level, we've actually seen very good allele editing across the patients that we have edited. Bone marrow is a part of the protocol. Those are set at future time points. 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 you know, truly recognizing the actual quantitation of fetal hemoglobin levels is best set around that four to six-month period, where historically we are seeing plateauing.
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. Maybe, Mark, do you want to comment on the specifics of the editing?
I think what we've mentioned in the past, we've exceeded 80% editing across a number of different cell populations, both normal sickle cell and TDT. 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've acquired that data.
Yeah. Yeah.
Thanks for your question. I just add on the editing point, right from clinical perspective, we also see that the high editing in the EDIT-301 editing of 30 CD34 cells in a clinical manufacture as well as for the peripheral nucleated cells from the first patient. 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. We are very pleased with the editing data.
Regarding the second patient, because there are reasons, as Gilmore mentioned, that one is that the hematological parameter will plateau, and secondly, it could be the very beginning of the data after the transfusion can be confounded by the red blood cell transfusion. We are 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 the subsequent patient.
Great. Thanks for all the color. Congrats again.
Thank you. Our next question comes from Steve Seedhouse at Raymond James. Steve, you may now unmute and ask your question.
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? Lastly, just wanted to confirm if these were the first two patients that were apheresed or if anyone who's been apheresed but ultimately not transplanted with edited cells. Thanks.
I certainly, I'll probably come back and ask you to repeat the second question. With regards 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. We're not actually sharing, you know, significant details on those data until we've actually dosed more patients where we can actually, you know, make reasonable inferences and correlations. Could you repeat your second question? I couldn't hear it.
Yeah. Apologies for that. It was just on the thrombopoietin use. It's a comment in graph in slide 10. Just if this is standard in these types of studies or something unique to your protocol?
You know, I didn't actually hear the word. Again, you said a word, but I can't hear it.
It's a comment on slide 10, just the three consecutive measures of platelet count starting at least seven days after last platelet transfusion and 10 days after TPO. I'm just curious if that TPO.
Yeah. In the slide.
Based on.
Yes, I see. Yes, I can hear. I apologize. I just couldn't hear what you were saying.
Based on?
My fault.
Yeah. Sorry, yeah. This is just the definition in the protocol and because when you have a platelet transfusion, you kinda confounding the counting of that, right? That's kinda with the condition. TPO, in case the TPO is needed, that also be part of that. For this patient, that is three cell count, the platelet count and meet the criteria and the day 37 being considered to be or 19 being considered platelet engraftment.
Again, this is a very standard approach, you know, for monitoring and calling platelet engraftment for stem cell transplantation.
Got it. That was my question. Thanks so much.
Yeah. Sorry for the, you know, yeah.
Thank you. Our next question comes from Dae Gon Ha at Stifel. Dae Gon, you may now unmute and ask your question.
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. Forget the slide number, but you were showing a natural history-ish, showing a correlation between HBF and the occurrence of the various VOEs. I think it ended on the X-axis about 25%. 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 in that paper, if you have that. 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.
Thanks very much, Dae Gon. With regard to the graph, I think it was actually on slide six. That is a graph that, you know, we used. It's rather nicely laid out. It's from a review from Steinberg et al. If you know, look at the data it cites and the published additional published data, this is where we kind of set the 30% threshold. The experience based on the natural variant that drives hereditary persistence of fetal hemoglobin, where that actually is co-inherited 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.
Uh, with regard to differentiation, um, uh, the, the duration of follow-up, uh, you know, to see impact on, uh, for example, robustness of the effects as well as the durable effects will actually be a matter of empiric observation. Um, and I, I think that is something that we will be able to talk about with more confidence as we extend our experience, uh, with, uh, human, uh, follow-up. And the same will be true around the impact of durability, uh, on, uh, vascular occlusive events.
Great. Thanks so much.
Thank you. Our next question comes from Mani Foroohar at SVB. Manny, you may now go ahead.
Hey, guys. Thanks for taking the question. Obviously, a lot of the nuances around the data, you've already answered. I'd like to follow up on Gena's question, as well as something that's been touched by a few others around clinical differentiation. Obviously, with only two patients, data looks quite 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? What would you guys be looking for over the next six, 12, 18, 24 months?
Where should our attention be focused as proof points for clinical differentiation?
Thanks very much, Manny. 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. I think that's a very important thing to remember. 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.
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. As a result, we'll be looking across a number of both hematologic parameters of hemolysis, as I said earlier, as well as clinical measures of end organ damage across multiple organ systems. I think it'll be the totality of the data that will actually help us determine differentiation, over the coming, you know, over the coming years.
Indeed, we actually suspect that that differentiation, could actually extend, beyond the 24 month period, and into, you know, longer, sort of medium to longer term follow-up.
That's helpful. If I might, if I can follow up, I guess the inverse of that question, which is, you know, presuming that when you achieve commercialization, there is a large portion 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?
Thanks very much. I'm actually going to share that question with Bais ong in a second. I think the key thing that, you know, certainly in my experience of therapeutic development and approvals is that the empiric data, as they evolve, have a enormous impact on how investigators, PIs, and experts think about, you know, the therapeutics and the parameters in which they're interested in making their clinical decisions and similarly for the patients. Bais ong, based on your interaction, you may want to share.
Yeah.
Your insights.
Absolutely. I mean, I had... Since I joined, I mean, in my prior time also, since I joined, we had a lot of interaction with the investigators as well as the hear from patient community. I can see that the feedback I heard was that there's enthusiasm for this gene editing program. I mean, one investigator mentioned that his patient is actually more interested into these autologous gene editing program than allogeneic transplant. Allogeneic transplant, as you mentioned earlier, have some drawbacks on that too, not only just finding the matched donor. That's kinda one thing. The other thing is that for this, for this patient community, not only investigators, even the patient community, they are very much interested into science, and they are also understand actually we have a different molecule, different approach, so they're interested in that too.
At least not only I hear from investigators, but also the patient community. I mean, as you probably well know, many rare disease community as the ones I work a lot on hemophilia, as well as sickle cell, they are very well educated. They are really getting to the science.
Thanks, guys. That's really helpful.
Thank you. This now concludes the Q&A portion of the webinar. Thank you for everybody, to everybody for joining. You may now disconnect.