Ladies and gentlemen, thank you for standing by, and welcome to the CTX-one Investor Event sponsored by Vertex and CRISPR Therapeutics. At this time, all participants' lines are in a listen only mode. After the speakers' presentation, there will be a question and answer Please be advised that today's conference maybe recorded. I would now like to hand the conference over to your speaker today, Mr. Michael Partridge, Senior Vice President of Investor Relations.
Good morning. This is Michael Partridge of Vertex. Susan Kim, Vice President of Investor Relations for CRISPR Therapeutics and I are pleased to introduce today's call, which will focus on the groundbreaking clinical data for our investigational gene editing treatment, CTX001, in the treatment of sickle cell disease and beta thalassemia. Providing prepared remarks on the call today are Doctor. Reshma Kewal Ramani, Vertex's CEO and President Doctor.
Haydar Frangul, Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and Doctor. Sam Kulkarni, Chief Executive Officer of CRISPR Therapeutics. Doctor. David Altschuler, Vertex's Executive Vice President of Global Research and Chief Scientific Officer, will join us for a Q and A session following their prepared remarks. We recommend that you access the webcast slides as you listen to this call.
This call is being recorded. A replay will be available on both the Vertex and CRISPR Therapeutics websites. We will make forward looking statements on this call that are subject to the risks and uncertainties discussed in our filings and CRISPR's filings with the Securities and Exchange Commission. These statements, including without limitation, those regarding expectations for the therapeutic value, development and commercial potential of CRISPRCas9 gene editing technologies and therapies, including CTX-one and the anticipated benefits of the collaboration between Vertex and CRISPR are based on management's current assumptions. Actual outcomes and events could differ materially.
I will now turn the call over to Doctor. Reshma Kewalramani.
Thanks, Michael. In October of this year, 2 pioneering scientists awoke to the news that the gene editing discovery they published in 2012 had won the world's most distinguished scientific recognition, the Nobel Prize in Chemistry. CRISPRCas9 gene editing technology is widely heralded as one of the greatest scientific and medical advances of our time, with the potential to realize the ambition that inherited genetic diseases can be cured with a one time gene editing treatment. And today, based on the clinical data for CTX-one, the potential to cure inherited diseases with the precise gene editing therapy is one step closer to becoming a reality. I am pleased to be here with our partner CRISPR Therapeutics and with Doctor.
Frangoule to review with you these data and our recent progress and upcoming milestones to bring CTX-one to people with beta thalassemia and sickle cell disease. The CTX-one clinical data presented as part of the ASH plenary session this past weekend and published simultaneously in the New England Journal of Medicine represent a medical breakthrough and underscore the transformative potential that gene editing hold in the future treatment of many serious diseases. Perhaps most importantly, these data show that CTX-one has the potential to be a one time functional cure for people living with sickle cell disease and beta thalassemia in the near term. As a result, we are advancing through clinical development with urgency and with the goal of bringing CTX-one to patients as soon as is possible. Doctor.
Frankel will review with you in detail these important data in just a moment, But I'd like to provide my perspective on the various reasons why we believe these data are important for patients, but also for Vertex and CRISPR Therapeutics. First, all 7 patients with beta thalassemia treated with CTX-one remain transfusion independent. And similarly, all 3 patients with sickle cell disease remain free of vaso occlusive or VOC pain crises. Frequent transfusions or pain crises are highly disruptive and debilitating for patients with these diseases. And the elimination of such events underscores both the medical importance of these data and the potential for CTX-one to significantly improve patients' lives.
2nd, the clinical response to CTX-one has been both durable and highly consistent across these patients. We see a rapid and substantial increase in total hemoglobin and hemoglobin F, and these increases have been sustained over time ranging from 3 months to well over a year for some patients. Specifically, a precise and permanent change to the DNA made through gene editing is expected to be durable over time as these cells following successful autologous bone marrow transplant and the clinical data generated to date for CTX-one strongly support this view. We will continue to follow these and additional patients to generate a complete picture of the overall safety and efficacy profile for the program. And finally, this program has been gaining momentum over the recent months in enrolling and dosing patients.
A total of 20 patients have been dosed across the 2 studies, including 13 patients with beta thalassemia and 7 with sickle cell disease, A key milestone that enabled increased momentum in enrollment and dosing was the progression of this program to concurrent enrollment and dosing in both studies earlier this year. We also amended the studies to include younger patients and for beta thalassemia to enroll patients with severe betazerobetazerobetazerobetazerogenotype.
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fast track, orphan drug and rare pediatric disease designations. And in Europe, we've received orphan drug designations in both diseases as well as priority medicines designation for sickle cell disease. Collectively, these designations indicate an appreciation of the high unmet need in beta thalassemia and sickle cell disease and the promise of CTX-one. These designations also provide us with increased regulatory interaction and input around key areas of interest for this program. While it is too early to outline in detail all the specific regulatory requirements for potential approval of CTX-one, we anticipate the key factors that regulators will want to evaluate include the size and duration of the safety database, the primary efficacy endpoint and the CMC requirements for commercial manufacturing.
Concerning commercial manufacturing, we recognize that the process and controls required for the manufacturer of CTX-one in clinical development and in commercial are of critical importance. Together with our partner CRISPR, our focus from the start of this program has been to build and scale a rigorous manufacturing process while reducing CMC complexities that could disrupt our progress towards commercialization of CTX-one. With that in mind, our manufacturing materials data generated from our ongoing studies and the manufacturing process used in clinical development will be used to support our marketing approval applications, including our BLA in the U. S. In summary, we are very pleased with the advancement of CTX-one development program and look forward to updating you with more details on our regulatory plans as the program progresses in the coming months.
I will conclude with just a few words on what CTX-one represents for Vertex and our continued growth beyond CF. Vertex is a portfolio of 1st in class programs in the clinic across 5 different disease areas. The most advanced of these pipeline programs is CTX-one, where together with CRISPR therapeutics, we've now established proof of concept in both beta thalassemia and sickle cell disease. To support development and commercialization of CTX-one and other nucleic acid based therapies, we are building industry leading capabilities and expertise across cell and genetic therapy site. Over the past few years, we have significantly increased our investments in these areas by acquiring or collaborating with many different companies, CRISPR, Moderna, Sema and others, fully aligned with our internal R and D strategy.
Our investments in cell and genetic therapies are broad and significant. And we believe the data for CTX-one are the first of many important updates to come from these efforts over the coming year that will further define the future of Vertex's pipeline across multiple serious diseases. With that, I will hand the call over to Doctor. Haydard Frangoule, who will review the CTX-one data as presented at ASH over the weekend. Doctor.
Frangou?
Thank you so much for having the opportunity to present the data. I'm going to go over the very exciting data we presented at ASH last Sunday in the plenary session on both CLIM-one hundred and eleven and CLIM-one hundred and twenty one. They are both FASES II international multicenter open label trials. They are CLIMB-one hundred and eleven is currently echoing patients ages 12 to 35 with transfusion dependent beta thalassemia including beta0 genotype. The primary endpoint of the thalassemia trial is the proportion of patients achieving sustained transfusion reduction of 50% for at least 6 months starting 3 months after CTX-one infusion.
For the CLIMB-one hundred and twenty one study for sickle cell patients, it's currently accruing patients 12 to 35 years of age with severe sickle cell disease and a history of at least 2 vaso occlusive crisis per year over the previous 2 years. And the primary endpoint for that clinical trial is the proportion of patients with a fetal hemoglobin of equal or greater to 20% sustained for at least 3 months starting 6 months after CTX-one infusion. Here I'm going to present data on the first ten patients infused with CTX-one. The principle here is that is naturally occurring genetic polymorphism in BCL11A, which is associated with elevation in fetal hemoglobin and decreased severity in both patients with transfusion dependent thalassemia as well as sickle cell disease. Bc11a suppresses expression of fetal hemoglobin.
In preclinical data editing of Bc11a resulted in reactivation of the gamma globin and expression and formation of fetal hemoglobin and this CDX-one is produced using in vivo editing of the erythroid enhancer region of BC11A in CD34 hematopoietic cells and reduces erythroid specific expression of BC11A. I'm going to start by presenting data on the 7 patients with beta thalassemia that have been in infused and have a minimum of 3 month follow-up. The genotype is listed on the slide here. But I just want to point out the 2 patients with the IBS 110 mutation, which is severe mutation in the beta globin gene and the one patient with beta0, beta0, which also a very severe phenotype of the disease. 5 female subjects were dosed and 2 male subjects.
The median age was 23 years and the patients received multiple transfusions per year prior to enrollment. You can see on the slide, the median per year number of packed red blood cells received is 33 ranging from 24 to 61 units per year. All patients collected peripheral blood stem cells in one mobilization cycle and the median cell product infused was 11,600,000 CD34 per kilogram ranging from 4.5 to 16.6. All patients achieved both neutrophil and platelet engraftment at 32 and 37 days respectively. All adverse events we observed on this clinical trial were generally consistent with myeloablation in autologous stem cell transplant.
The majority of AEs occurred within the 1st 60 days after infusing CTX-one. Two patients experienced combined total 5 serious adverse events related to or possibly related to B Cellspan including veno occlusive disease of the liver in 2 patients, febrianeutropenia, there were 2 events in 1 patient and colitis, all of which has resolved. One patient experienced a serious adverse events related or possibly related to CTX-one include headache, hemathegocytic lymphocytosis, acute respiratory distress syndrome and idiopathic pneumonia syndrome. All SAEs occurred in the context of HLH in that patient and resolved. No CTX-one related serious adverse events were reported in the other 6 patients.
Now I'd like to present the clinical outcome data for the 7 patients. As you can see from this slide, there was early and sustained increase in total hemoglobin and fetal hemoglobin in all patients. This is individual patient data. And again, I want to point out patient number 1 and patient number 6, both of which have the severe beta globin mutation, IDS-one hundred and ten and both patients at last fall off had normal hemoglobin. I also want to point out the exciting results we are seeing in the beta0, beta0 patients we enrolled and at the 3 month mark, she had a hemoglobin of 9.7 and because I treated her in my sensor, I can tell you that when I saw her at the 4 month mark, her hemoglobin was 11.5 and she continues to be transfusion independent.
This slide talk about the duration of transfusion independence. So the elevation in the fetal hemoglobin we observed in our patients actually translated into transfusion independence in all patients. This slide shows the number of transfusions patients received on the left side, the number of transfusions patients received in the year prior to infusion of CPX-one and on the right hand is the follow-up for all patients. And as you can see with a follow-up of 1.8 to 20.5 months, all patients remain transfusion independent. Now I want to switch gears and talk about the 3 patients with sickle cell disease that have been infused and we are reporting on with a 3 month follow-up.
They were 2 female subjects and 1 male subject. The median age was 22 and the number of vaso occlusive crisis per year averaged around 7 vaso occlusive crisis per year in the last 2 years prior to enrollment. 2 patients require 2 mobilization cycles to achieve the target cell dose and one patient collected in 1 mobilization cycle. The drug product cell dose infused was range from 3,100,000 to 3,900,000 per kilogram. All patients achieved both neutrophil and platelet engraftment at 22 30 days respectively.
Next slide talks about the adverse events. Again, all adverse events were generally consistent with myeloablation and autologous stem cell transplant. Majority of AEs occurred within the 1st 60 days after CTX-one infusion. 1 patient experienced serious adverse events related to paraxypher including chest pain, neck pain, headache and abdominal pain, all of which resolved. Post CTS-one infusion, one patient experienced a serious adverse event including sepsis related to Bsulfan, colitis and abdominal pain both are related to any study drug.
None of the serious adverse events in the patients were related to CTX-one. The next slide we present the clinical outcome data for the 3 patients. As you can see, there was clinically meaningful elevation in fetal hemoglobin and total hemoglobin that was achieved early and sustained over time. As you can see, patient number 1 at last follow-up at 15 months had a hemoglobin of 12% with 43% fetal hemoglobin. Patient 2 at the 6 month mark had a hemoglobin of 11.5% with 48% fetal hemoglobin, just noting that the patient's baseline hemoglobin was 6 and the 3rd patient at 3 month follow-up had a hemoglobin of 13.2 with 31% fetal hemoglobin.
So as you can see from this slide that the fetal hemoglobin range from 31% to 48% in our dosed patients. The elevation of fetal hemoglobin we observed in all Phe patients and the elevation in total hemoglobin was only was also associated with clinical benefit in all patients. This slide shows the number of vaso occlusive crisis each patient experienced in the year prior to enrollment, prior to dosing of CTX-one. For patient 1, she had 7 vaso occlusive crisis the year before and as you can see with a follow-up of 16.6 months, she has not experienced any serious adverse events or vaso occlusive crisis during that time. None of these 3 patients with a follow-up of 3.8 to 16.6 months experienced any vaso occlusive crisis related to sickle cell disease, which is amazing.
All patients had undetectable haptoglobin indicating hemolysis of the red blood cells. And I'm happy to report that all patients now have detectable haptoglobin after infusion and improved LDH indicating stabilization of the red blood cells and decrease or no evidence of hemolysis in the patients. In conclusion, the 10 patients treated with CTX-one have been followed for 3.8 months to 21.5 months and have stopped transfusions in the case of beta thalassemia patients and none of the patients with sickle cell disease experienced any vaso occlusive crisis. Overall safety profile is generally consistent with myeloablation conditioning and autologous bone marrow transplantation. Clinically meaningful hemoglobin F and total hemoglobin levels are observed early and maintained across all ten patients.
Clinical proof of concept for CTX-one has now been demonstrated for both beta thalassemia and sickle cell disease and these data demonstrate that CTX-one is a potential functional cure for treatment of beta thalassemia and sickle cell disease. Thank you.
Thank you, Doctor. Frankel. Less than a decade ago, our scientific founder, Doctor. Emmanuel Charpentier made her Nobel Prize winning discovery of CRISPR Cas9 editing. It was immediately recognized as a revolutionary technology and there was speculation that it would someday benefit human health.
Today, we see more evidence that this promise is becoming a reality. The updated data we shared at ASH are a powerful proof of concept for CTX-one, which we believe will advance us toward a new class of CRISPRCas9 based medicines to treat serious diseases. Beyond CTF-one, we at CRISPR Therapeutics have built a broad portfolio across 3 additional focus areas: immuno oncology, regenerative medicine and in vivo therapeutics. Earlier this fall, we released our first data on CTX-one hundred and ten, an allogeneic CAR T therapy for CD19 positive malignancies, showing early signs of efficacy on par with autologous CAR T. Our regenerative medicine program in type 1 diabetes is progressing rapidly towards initiating clinical trials next year and we continue to progress our efforts using in vivo approaches.
Taken together, we are building the preeminent gene editing company with multiple groundbreaking programs having achieved or nearing clinical proof of concept and a robust early stage pipeline. Our vision is to become a fully integrated company commercializing multiple transformative medicines for serious diseases. But today, we are thrilled with the new data released on CTX-one. We believe this therapy has best in class potential due to a number of its unique characteristics. As you know, CTX-one works by reawakening fetal hemoglobin, mimicking naturally occurring elevations of fetal hemoglobin that have been shown to reduce or eliminate the symptoms of beta thalassemia and sickle cell disease.
A single precise edit to the genome is all that is required to achieve the remarkable results that we have seen to date with CTX-one. We believe that the addressable market for best in class potentially curative therapy such as CTX-one can be very significant in the near term and maybe expanded even further with the benefit of improved conditioning regimens. We also recognize that CTX-one may benefit patient populations who have historically been underserved and have had limited choices in terms of therapeutic interventions. We believe that there is strong support from the health system to address these diseases with CTX-one, given that it's not only brings value to patients, but also to the health system by reducing the burden of chronic healthcare utilization. And lastly, by combining the joint capabilities of CRISPR and Vertex, we are well positioned to scale up our manufacturing and our commercial infrastructure to meet the needs of patients globally and have a broad and transformative impact on these patient populations.
We also believe that it can impact a large number of patients from both sickle cell disease and beta thalassemia with CTX-one in the near term. In the U. S. And EU, there are approximately 150,000 patients with sickle cell disease and approximately 16,000 patients with beta thalassemia. And a significant proportion of these patients have severe forms of their disease that require frequent medical intervention and shortened life expectancy.
Even assuming current conditioning regimens, we believe that people with severe disease will be the most likely candidates for CTX-one. And we estimate that this population to be approximately 25,000 with severe sickle cell disease and approximately 7,000 patients with beta thalassemia across the U. S. And EU. Patients with sickle cell disease, as you know, are predominantly in the U.
S. Where the disease is more prevalent, whereas the beta thalassemia, more patients are in Europe. Taken together, this population of over 30,000 patients represents a significant market opportunity for CTX-one. These estimates assume current conditioning regimens, but progress is being made towards novel regimens that are gentler than those used today. We and others are working on several different approaches in this area, some of which are already in clinical trials.
These new targeted approaches could offer better tolerability, shorter hospital stays and accessibility at a broader network of treating facilities, which could enable all symptomatic beta thalassemia or sickle cell patients to seek a potentially curative therapy such as CTX-one. On behalf of everyone on the CRISPR and VERDEX teams, I'd like to thank all the patients and caregivers for their courage and support in advancing the CTF-one program. This is an exciting time for CRISPR and for Vertex, but most importantly for all those living with beta thalassemia or sickle cell disease who now have renewed hope in the future treatment of their disease. Reshma, Doctor. Frangul, David and I are now happy to answer any of your questions.
Thank you. Our first question comes from Salveen Richter with Goldman Sachs. Your line is open.
Thank you and congratulations on the data. Two questions for me. Doctor. Frankel, how do you see yourself incorporating the gene editing therapy in your treatment paradigm? And do you envision using it only in severe patients or would you be interested in also going to the mild to moderate patient population?
And then for Vertex and CRISPR, I think you just mentioned some novel approaches here with these programs. Could you just help us understand as you look to optimize the program longer term what you're doing here, specifically around the preconditioning regimen and also whether there is a next generation in vivo editing program on the horizon? Thank you.
Hey, good morning, Salveen. This is Reshma. Let me take the second part of your question first, and then I'm going to ask Doctor. Frangoule to comment on your very good question around the potential eligible patient population that I think Sam outlined, but I think Doctor. Frangoule with his clinical experience can certainly fill in a little bit more color.
So Salveen, our intent here is to commercialize the CTX-one program with the conditioning regimen that we used in clinical development, that is to say with busulfan conditioning. It's a single agent myeloablative regimen. It's commonly used, well understood. And that is indeed the regimen that's led to these really just remarkable results. We are actively working with CRISPR, we at Vertex along with partner companies on gentler regimens.
And I'm going to ask David to comment on our collaboration with Molecular Templates. And after David speaks, I'm going to ask Doctor. Frankel to comment on the patients. David, do you want to just say a couple of words about the GENTLER regimens with molecular templates as an example?
Yes. Thank you, Reshma. As mentioned, both Vertex and CRISPR as well as others in the field are working to find gentler conditioning regimens. We established a collaboration with Molecular Templates in November of 2019 to discover and develop novel targeted conditioning regimens. That's a program in the discovery phase and we look forward to updating you as it moves closer to the clinic.
We also have internal activities to work towards gentler approaches to delivering this to patients, and we look forward to telling about you those in the future.
Doctor. Frenkel, could you make a comment about what you see as the eligible population based on your clinical experience?
Well, thank you for the question. I just want to mention that there are 100, if not 1000 of patients that can benefit from curative or potentially functionally curative therapies for sickle cell disease. And as you know, more than 80% of those patients lack a potential allogeneic donor in the family, basically a fully matched donor. So I anticipate as the efficacy and safety data is followed over time for CTF-one that it might provide help to a lot of patients with sickle cell disease that are suffering from their illness and do not have a good option for treatment. So I see this that can expand the use of autologous cells to treat patients with sickle cell disease.
Just to round it up before we get to the next question, Salveen, I think you know this, but I'll just say for others on the line, the big impediment to bone marrow transplant for sickle cell or beta cell are really 2 big things. 1 is Doctor. Frangoule outlined the lack of a suitable donor. There are only 20% of patients who can find a related match donor. That's one important point.
But the second important point, even if you can find a donor, there is a very important graft versus host disease that can develop and that is really quite limiting. Both of those are obviously overcome by autologous CTX-one BMT.
Thank you.
Thank you. Our next question comes from Geoff Meacham with Bank of America. Your line is open.
Hey, guys. Thanks so much for the question and also congrats on the data. Just have a couple of quick ones. Reshma, I know you mentioned the regulatory path and this is probably the most common investor question that we get on 1. Is there an efficacy threshold that you've discussed with FDA that would allow for a filing on a smaller number of patients or is the size of the database not as important as the treatment effect?
And then the second question is, when you look at the patients with the longest follow-up, are there lessons to be learned as to how durable the benefit could be? And what is your expectation? How does this inform your ultimate pricing decisions down the road? Thank you very much.
Yes. Hey, Jeff, thanks so much for the congratulatory words. We are really excited about these data. With regard to the regulatory pathway, as I said in my prepared remarks, we have started our conversations with the regulators, but we have not concluded them. We have every designation you could imagine with both the U.
S. Regulators and the Europeans. And so we have opportunity to have productive and frequent conversations, and we're certainly going to take full advantage of that. You are right to point out that the treatment effect, the benefit risk profile that you see, the safety profile that you see all influences exactly what the package is that we would be submitting and what the regulators will be accepting and expecting. We just haven't gone through all of those discussions yet.
But the data really just are I couldn't imagine better data, more positive of a benefit risk profile. And so we're going to be working with urgency and with the expectation that we are going to be able to move forward rapidly to bring this to patients. With regard to what did we learn from the first few patients, a few important lessons. As we expected, the impact is significant in both sickle cell and beta cell. The first patients in each program are now out 12 months or greater and the effect is durable, hemoglobin F levels and total hemoglobin.
And we've been really pleased to see the side effect profile. That has just been wonderful to see.
Okay. Thank you.
Thank you. Our next question comes from Jen Wang with Barclays. Your line is open.
Thank you for taking my questions. Also I wanted to add my congratulations to the great data. So I have a few questions regarding the data. First, just wondering if you can both beta cell and sickle cell reach almost like 100% F positive cells. Just wondering what is the definition of F positive cells aiming fetal globin threshold to define as F positive?
And the second is regarding the editing efficiency. You also show very impressive editing efficiency. Just wondering, was there monolithic editing or are these a bialytic editing? And last quick question with regard for Doctor. Sango.
You mentioned that beta thalassemia patient 7 reached at the month 4 reached 11.5 total hemoglobin. Just wondering what is the fetal globin level for that patient?
All right, Gina. You have packed in a few different questions in there. Let's parse it out in the following way. I'm going to ask David Altschuler to explain how we measure F cells. And there is obviously a difference between F cell percentages that we talk about and hemoglobin F percent.
So I'm going to ask David to tell you about that, as well as the editing efficiency. And then certainly, Doctor. Frangoule, about the question you have on how our patient is doing. But without stealing thunder from Doctor. Frangoule, I'll tell you the patient is doing exceptionally well.
David, let's start with you.
Thank you for the question. So there are a couple of questions there. One is about the difference between F cells and the level of hemoglobin and whether or not there's a threshold. And let me say that the two measures are F cells are those that you can measure the percentage of cells that express hemoglobin F and we would like that to be as high as possible what's called pan cellular because you'd like to have all the cells be corrected in the circulation of patients that have been described, nearly 100% of the cells express fetal globin. There's also a measure which is the percentage of hemoglobin that is the fetal globin, which in the case of sickle cell, as you can see in the data, is in the range of 30% to 50% and in the patients with TDT nears 100% as expected because in thalassemia, the patients don't make any hemoglobin on their own.
And finally, I'd say, and then Doctor. Frankel could comment, that the history in the field is that the levels we're seeing in sickle cell are consistent with the levels of hemoglobin seen in people who have hereditary persistence of fetal globin. And that is a safe and successful when people have those high levels, those levels of fetal globin, they do very well in natural history. So that and then second of all, there are people in the literature who have been described, who have up to 100% fetal globin and they also are healthy and do well. So we believe that the high levels of fetal globin we're seeing are desirable and expected to bring clinical benefit to people.
There's no level too high we're aware of. I'll let Doctor. Franghoul comment.
Much for the question. We are very excited about our patient number 7 on the trial with beta0beta0. And to answer your question at the 4 month mark, she had 74% fetal and 25 percent A hemoglobin reflecting the lost transfusion, which happened at the 2 month mark. I'm glad to say that she is doing very well and she's coming to our center next week for her month 5 and she remains transfusion independent, which is in my mind extremely great results we are seeing in the beta0, beta0 patient. Thank you.
Thank you.
Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is open.
Hi, good morning everyone and much congrats on the updates. Thanks for taking my question. So first question is, And thanks for taking
my question. So first
question is, just wondering
if you
could talk more about the overall product and treatment consistency and how this compares with competitors and maybe provide some perspective on how doctors and regulators perceive this?
Yes. Hey, thanks so much. I think that the overarching question here is how do we view the CTX-one results and can we provide some context when we look at the field in general? And maybe Sam and I will tag team this and I'll ask Sam to make some comments about the field in general. As I said in my prepared remarks, we couldn't ask for better results.
And I mean that not only in terms of efficacy, but surely in terms of efficacy, all patients that we presented in the beta thalassemia cohort are free of transfusions. All patients that we presented in the sickle cell cohort are free of vaso occlusive crises. These are the key outcomes that you're looking for. This is what determines the health and well-being of the patients. But I'm also really very pleased with the safety profile of the medicine.
And I'm really very pleased with the enrollment momentum and the reception that the data has received from physicians. As I said, we haven't had our conversations with the regulators just yet to conclude on exactly what the data package would look like. But whenever you think about filing in the regulatory package, the strength of the data, safety, efficacy and the benefit risk profile are key. And as I said, I just don't think the data could look any better. Sam, do you want to make a few comments about the competitive landscape?
Yes. Thanks, Reshma and Maury, thanks for the question. I actually look at that word consistency in 2 ways. 1, obviously, we're very pleased with the data we're seeing and how consistent the effect is across patients, as Reshma mentioned, and if you look at the patterns of the fetal hemoglobin elevation. The other part I think that gives us a big competitive advantage is consistency from a manufacturing standpoint as well.
Right from the get go, we've designed
our manufacturing process in a way where we can
scale up from clinical tweaks we make. Generally, we kept our process consistent, which is, I tweaks we make, generally we kept our process consistent, which is going to be an advantage as we move towards registration and ultimately towards commercialization. And as I look at the field, I think it's hard for us to comment on exactly on the competitor data and that's generally not our practice. But using CRISPRCas9, we're making a single precise and permanent edit to the genome is going to be an advantage because the process is more facile, it's simpler, it's easier to scale up, the cells are healthy. And I think compared to other approaches that use lentivirus where there's random integration into the genome, which brings inherent variability in the process, I think we're well positioned to be best in class.
Obviously, we need to execute on the program, but I think the fundamentals are there with the data we're seeing today and the fact that we have this fast sell process that sets us up well relative to the field.
Hey, Reshma, it's Mike Yee. Can I pop in with a follow-up there?
Mike, it's nice to hear your voice, of course.
So thanks for the comments on the regulatory part. What can we learn from the regulatory comments that one
of the gene therapy companies has obviously publicly commented on? And what can we learn from what they have to do? And when would you be able to come back to The Street and tell us, what you would have to do? Thanks.
Yes. Mike, it's a really great question. I anticipate that in the coming months, we're going to be able to come back to you and share what we think the regulatory pathway will look like. In terms of what have we learned, a few things, great data in areas of high unmet need are something that we are interested in moving forward to patients quickly and something that regulatory agencies around the world are interested in moving forward to patients rapidly. The keys here are the size and duration of the safety database.
We just have to have that discussion. The enrollment and dosing momentum is very important, obviously, because that brings us to the end faster. And one point that Sam touched on, I think, is critically important, which is manufacturing. As Sam said, we have designed our manufacturing from the get go to be consistent with what we're going to manufacture in the commercial side of this. And I think that's very, very helpful.
Lastly, when you look at the field, just open the aperture and look at the field of genetic therapies as a whole, regardless of the disease in question and regardless of the exact nucleic acid therapy being used, what you see is a filing package that measures in the dozens, not in the hundreds and certainly not in the thousands.
Yes. Thank you very much and congrats to you guys and to Sam and CRISPR. Thank you.
Thanks Mike.
Thank you. Our next question comes from Liisa Bayko with Evercore. Your line is open.
Hi. And I want to offer my congratulations as well, really great data. As we kind of think about the kind of potential size of this opportunity for Vertex and for CRISPR, I wanted to better understand sort of the flow of patients and how what is the capacity in the healthcare system? This is obviously heavy on resources in terms of like number of patients per year that you could really address with CTX001 in terms of the kind of healthcare resources required? And also, have you done any work on access to therapy in this population?
And what does the payer mix look like? Just things to consider as we're trying to understand the size of this really medically meaningful advancement. Thanks.
Yes. Thank you for that question, Lisa. And I'll start with some remarks and also see Freshman has to add anything. I'll start with your second question first on the access. I think as you heard from Doctor.
Frangou and Reshma, we have sort of this trifecta here, right? You have a patient population that has is severely underserved and there's a strong unmet need. These are patients that have not had a disease modifying therapy, let alone a potentially lifetime cure. You have a relatively large patient population here, both in the U. S.
And Europe. And moreover, I think what you have is a therapy that could ultimately save health systems cost because of all the reduction in the chronic healthcare burden. You had recent publications even from CMS showing what the healthcare burden is from sickle cell disease where patients are going in for a number of hospitalizations and have a number of crises per year. So with that, I think we believe that there will be strong support from the health system from an access standpoint. Obviously, there's a lot of work to do, I think, in the U.
S. Primarily. You're talking about a Medicaid population. And in Europe, obviously, there is different payers based on each country and the payer landscape is different. But I just think that there's going to be strong support and we started some of that work already as we build towards build our commercial capabilities jointly.
To your first question on the patient flow, this is a large number of patients that may be eligible for this therapy and may seek this therapy. In the U. S. Alone, we said that a large fraction of the 100,000 or so sickle patients and between the U. S.
And Europe, there's 150,000 sickle patients and nearly 25,000 of them are severe enough that would seek this therapy. And what you have in the health system today is, you may ask the question, why are there not more allogeneic transplants? And the reason for that is what Reshma was mentioning before, you don't have matched donors and you have the risk of graft versus host disease. But otherwise, I think the system will equip itself to be able to do a number of these transplants, a large number of these transplants. Obviously, we have to support this health system and from a company standpoint, to make sure there are the resources and necessary and all the training required to be able to deal with a large number of patients, but that's imminently doable.
And I think we can scale up our patient experience and our support systems to be able to meet the needs of hundreds of patients, if not thousands.
Sam, I really don't have much yet. I think you've covered it really well. I think that clearly, this is a more resource intensive, a shift perhaps in where the patients are cared for today to where they may need their care in the future, I. E, in the setting of having to come in house, receive a bone marrow transplant. That is absolutely true.
However, what that means is that what we are looking at is potentially a one and done functional cure. And that means no frequent ER visits for pain crises or for IV fluids or for transfusions. It means no more visits to the ER for pain medicines. It means no more hospitalizations and it means people being able to go and live their life. So I agree with Sam very much that changes in the setting of care may be occurring, But I think that in the U.
S. And in Western parts of the world that this is going to be something that can be accommodated for the benefits that people receive.
Thank you very much.
Thank you. Our next question comes from Paul Matteis with Stifel. Your line is open.
Great. Thanks so much. And let me add my congrats on the data. I had one regulatory question and one quick safety question. On the regulatory side, I know you're engaging with the FDA, but can you talk about the work you're doing with release assays in cellular characterization?
And what your thinking is on kind of the regulatory hurdle there and what you need to show? And then on the safety side, I don't know and I'd be curious on Doctor. Frangoule's view as well as to whether or not this is relevant. But can you speak a little bit more about what you're seeing with platelets? I saw that you've disclosed some data that's encouraging and engraftment, but the hurdle in that data, if I'm reading this right, is 50,000, which is still in the thrombocytopenia range.
So maybe just give any color you can on whether or not this is a concern at all? Thanks so much.
Yes. This is Reshma. Maybe I'll just take the second question first. Paul, on all of the data that we see, laboratory as well as patients visits in follow-up, as well as imaging and fundamentally all assessments of patients, we don't see any areas of concern in the data that we have. Everything looks good to date.
With regard to the question around regulatory, and I think it's this is about CMC and exactly how we're thinking about this. I know Sam has some comments that he'd like to make on that front. Sam?
Yes. Thank you, Reshma, and thanks for the question. I think one of the benefits we have here in terms of regulatory interactions is having the RMAT designation and prime designations, which have allowed us to have a lot of seamless dialogue with the regulators who have all been very supportive and collaborative. From a CMC standpoint, as I said earlier, one of the advantages we have with the CRISPR platform, while it's the most cutting edge and novel platform, in many ways it's simpler than some of the older generation platforms. Take for instance characterization of the Cas9 protein.
This is a simple protein manufacturing and it's a very consistent process and we can characterize the starting components. With the assays, obviously, again, we have to make sure that all the assays meet all the requirements, but that's how we've designed it right from the get go to make sure that we've in the clinical trials incorporated the assays that ultimately are scalable into commercial realm. So we're confident that we can meet all the needs and thresholds that the regulators set and that's been a collaborative process with the regulators with frequent discussions and we'll update you more as we go along in the program.
Thanks.
Thank you. Our next question comes from Phil Nadeau with Cowen and Company. Your line is open.
Good morning. Thanks for Another regulatory question. Just in terms of the following, appreciating that you haven't completed the discussions with the FDA yet. What do you think will be limiting? Will it be accumulation of a sufficient number of patients with sufficient follow-up?
Or is it something like manufacturing scale up and assay development?
Yes. That's a great question, Phil. Genuinely, I don't have concerns. I don't see this as a filing where we are in one place and the regulators are in another. This is a high unmet need population.
As Sam mentioned, there really aren't any therapies that treat the underlying cause of disease, and there certainly aren't any therapies that cure the disease and that's kind of what we're looking at here. There's absolutely going to be a need to have the right number of patients and duration of follow-up. That's a very reasonable expectation. There's going to be discussions around exactly what the endpoint needs to be and how long that endpoint needs to be seen for what duration of time and the CMC questions that we've spoken of on this conference. But they are expected, and we're looking forward to going through the regulatory interactions and being able to update you on exactly what our agreements are.
We're simply not there yet, but I am looking forward to those interactions. I'm equally looking forward to
updating you.
That's helpful. Thanks for taking my question and congrats again on the day.
Okay. Thanks so much.
Thank you. Our next question comes from Evan Sigerman with Credit Suisse. Your line is open.
Hi there. Thank you so much for taking my question. Really congrats on
the data. It's really striking how
the most interesting that I've seen it asked. So for Doctor. Frangol, looking ahead, you had talked about potentially using different conditioning regimens kind of in to make it more applicable or more accessible. I was wondering if you could speak more to that and how impactful is the current conditioning regimen and how much how better do you need to get the conditioning regimen to maybe expand the kind of the applicability to more than just the most severe patients? Thank you.
Steven, thanks for those kind words. This is Reshma. Let me maybe kick it off and then I'll ask Doctor. Frangoule to comment. I want to be sure that we are very clear about the fact that the current regimen, the one that we're using in clinical development is busulfan based.
And again, the reason for that is that it's a single agent myeloblative therapy that is well understood and commonly used. It is indeed the conditioning regimen that's led to these remarkable results and it is the regimen that we intend to file with. The question you asked about how do patients fare with this, Doctor. Fango has talked to me about this before and I really appreciate his words about how the patients have tolerated the regimen, the engraftment and I'm going to turn it over to him for that. But be sure also Evan that in a go forward basis after the initial approval, we're already working, as you heard from Sam and from David, we're already working on gentler regimens.
And that is something that we think is important in the longer term to make this therapy really convenient, not only applicable, but very convenient for our patients over the long haul. Doctor. Pringle, do you want to speak a little bit about the conditioning regimen, how you've seen the patients do and just round out that question?
Well, thank you for the question. So when we are enrolling patients and explaining to them the preparative regimen with Bsultan only, we really have not met significant resistance from the patient to enroll on the study. So that's one point. The second point is when we have given this regimen as a single agent to the patients we have treated, it has been very well tolerated and the patients have not really developed any significant side effects that gives us red flags that we should not be continuing using this regimen for now until some alternative regimen is tested. So I'm very comfortable with the B cell ten single agent for the time being for the patients we are using and we are seeing great results with it as you saw.
Thank you.
Great. Thanks so much.
Operator, this is Michael Partridge. We're coming up on the hour, so we have time for just one more quick question.
Okay. Our last question comes from Matthew Harrison with Morgan Stanley. Your line is open.
Hey, Matt, unfortunately, your phone is breaking up. I think you have a CMC question. It's very difficult to hear.
This is Reshma. To Matt, I'm sorry, we really just couldn't hear any part of the question. Maybe given the time, we'll just take a moment to say thank you for joining us today. Obviously, we're excited about this data. We look forward to updating you in the coming months, and I'll ask Sam to make some closing remarks.
Yes. Thank you, Reshma. We're equally excited here. I think the collaboration between CRISPR and Vertex is going really well. We're operating with a great sense of urgency given that these patients don't have a therapy and this could be transformative for these patients.
And we look forward to updating you more. But we will certainly look back at this time as a very important time where we disclose proof of concept data that's going to change the paradigm of medicine. Great. Thank you, everyone.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.