welcome, ladies and gentlemen, to the CRISPR Therapeutics Clinical Update Conference Call. At this time, I would like to inform that this conference is being recorded and that all participants are in a listen only mode. At the request of the company, we will open up the call for a short period at the end of the presentation. I would like to introduce Susan Kim, CRISPR Therapeutics' Vice President of Adelpric Communications. Please go ahead.
Good morning and thank you for joining us as we report results from our ongoing base of CTX-one for the treatment of beta and severe sickle cell disease. Joining me this morning are Sam Pokarney, Chief Executive Officer and Tony Ho. We recommend that you access the webcast slides on our website as you listen to this call. This call is recorded and a replay will be available on our website. In today's call, we will be making certain forward looking statements.
These statements may include statements regarding amongst the efficacy and safety of our product candidates, our research and development plans, regulatory plans and report additional data. These forward looking current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause us to differ materially from those contained in the forward looking statements. These and other risks are discretailings made with the SEC, including our quarterly and annual reports. You are cautioned not to place undue or looking statements, which are only made as of today's date. The company disclaims any obligation to update this call.
With that, I'm pleased to turn the call over to Sam Kulkarni, our CEO, who will make some introductory remarks.
Thank Good morning and thank you all for joining us today. Earlier this morning, we reported the first clinical results from 2 patients with severe hemoglobinopathies, PTX-one, a CRISPRCas9 based investigational therapy that we are developing together with pharmaceuticals. This is a significant milestone for our company as well as the entire field first report of clinical data from a company sponsored trial of a CRISPRCas9 based therapy. Less than a decade ago, when CRISPRCas9 was acquired by our scientific founder, Doctor. Emmanuel Sharp NTA, it was immediately recognized as a revolutionary technology, but it was not known how it would benefit human health.
Today, we show that this promise is becoming a reality. The results so far early indicate that CTX-one has the potential to be a curative approach for cell disease and beta thalassemia. Our Head of R and D will now go through a brief presentation of the data.
Thank you, Sam. As manco cell disease and beta thalassemia are severe genetic disorders that affect hemoglobin, aging in the blood responsible for transporting oxygen throughout the body. Millions of people worldwide have hemoglobinopathies and they result in significant morbidity, a heavy burden of care throughout life, reduced life expectancy. There are very modifying approaches available to treat these disorders and a functionally curative approach to gene editing could have an enormous impact for these patients. We are aiming to making a single genetic edit in the blood forming stem cells of the patient using CRISPRCas9.
We carefully designed this edit to increase levels of fetal hemoglobin, a protein that can substitute hemoglobin that causes both sickle cell diseaseemia. As shown on Slide 3, this approach is supported by decades of rare patients who have naturally high levels of fetal hemoglobin that from disease symptoms without any harmful side effects. In fact, if the level is completely asymptomatic, We are using CRISPRCas9 to mimic these protected genetics for not so fortunate as to have them occur naturally. Over the past several years in our research labs, we screened numerous ways of using CRISPRCas9 to increase levels and finally selected CTX001 as our lead candidate. As shown on Slide 4, this approach makes a single double stranded break in a non coding region of the BCD, which is known to regulate fetal hemoglobin levels specifically in red blood cells.
In this manner, we enhanced fetal hemoglobin production to protect against these disease. As Slide 5 shows, we have taken this approach into the clinic at multiple sites worldwide through our Phase onetwo CLIMB trials. CLIMB Cell-one hundred and eleven treats adult patients with transfusion dependent beta thalassemia and CLIMB SYCL-1 hundred and twenty one treats adult patients with severe sickle cell disease. The primary endpoint for the thalassemia trial is reduction in transfusion burden, whereas the primary endpoint for the sickle is the level of fetal hemoglobin produced. Slide 6 demonstrates the treatment approach which is similar in the two trials.
Both occur in the context of an autologous stem cell transplantation. A patient's stem cell are collected and shipped to our manufacturing facility where they are edited at the target locus using CRISPR Cas9. They are then frozen and shipped back to the treatment center before the added cells are infused. Once the added cells engraft successfully and reconstitute the patient's blood system, a process that typically takes 3 to 6 where patient can be discharged with periodic follow ups. On Slide 7, we transitioned to the clinical data on the first patient treated.
The patient had transfusion dependent to beta thalassemia of the beta0IV10 genotype and a significant transfusion burden requiring an average of 16.5 transfusions per year. Following infusion, the patient has vessel and platelet engraftments at days 33 and 37 respectively. The safety profile for this patient was consistent with busulfan conditioning and there were no adverse event considered related to CTX001. Serious adverse events occurred during the post transplantation neutropenic period and were not considered related to CTX001. The patient experienced veno occlusive liver disease that was attributed to Bussulfan condition both of which subsequently resolved.
On Slide 8, you can see that following CTX-one infusion, the patient demonstrated a notable increase in the fetal hemoglobin level began to rise at month 2 and increased to stable level above 10 gram per deciliter by 4 months post infusion. The last BOS transfusion for this patient was a 1 month post transfusion and as expected the transfused hemoglobin A declined from this point to a level less than 1 gram per deciliter. The patient has maintained total hemoglobin levels above 11 without transfusions, suggesting that the increase in fetal hemoglobin is sufficient to eliminate the need for transfusions. The patient started phlebotomy and iron clation at 3 6 months post transplant play in order to address the residual iron overload caused by the disease. Slide 9 shows the red blood cells in this patient demonstrate a highly pan cellular expression of fetal hemoglobin, 9.8% of cell positive for fetal hemoglobin at 9 months post transplantation.
Overall, these data suggest that this patient who previously required more than one transfusion per month and is being similar to a beta0 beta0 patient has now achieved transfusion independent due to the treatment with CTX001. On Slide 10, we transition to data on the person who at the time of consent was a 33 year old woman with severe sickle cell anemia and who had a historical rate of 7th severe basal occlusive crisis or VOC per year. The patient successfully achieved engraftment at day 30 after CTX-one infusion. The safety profile for this patient was also consistent with spousofen conditioning. There were 3 serious adverse events sepsis, cholelithiasis and pain, all have resolved and were not considered related to CTX-one.
Slide 11 shows that this patient also demonstrated a notable hemoglobin in the mice following transplantation with CTX-one. Prior to infusion, the patient received exchange transfusion which reduced the level of sickle hemoglobin or from 74% at baseline to 0% post transplantation. These transfusions were stopped at approximately 2 regions and subsequently the transfused hemoglobin A has decreased steadily. At 4 months post transplantation, fetal hemoglobin represented 46.6 percent of total hemoglobin. The total hemoglobin in this patient significantly from baseline level of 7.2gramto11.3grams per deciliter at 4 months post transplantation.
There have been no VOCs reported in the 4 months following transplantation. The percentage of sales expressing fetal hemoglobin has increased steadily post transplantation to 94.7% at 4 months and is continuing to increase as can be 12. We believe that this pan cellularity of fetal hemoglobin is highly desirable since it may ensure that the vast majority of red blood cells are prevented from sickling and causing the symptom of To summarize on Slide 13, we have reported initial clinical data on the first two patients, one with beta thalassemia and one with sickle cell disease that have been treated with CTX001. Key profile we observed is consistent with myeloablative busulfan conditioning and successful engraftment was achieved in both patients. The patient with beta thalassemia re infusion prior to treatment and has now been transfusion free for approximately 8 months.
This is likely due to the high levels greater than 10 grams per deciliter of fetal hemoglobin being produced due to the CTX-one. Similarly, the patient with sickle cell disease has experienced no VOCs in the 1st 4 months after treatment compared to a baseline rate of 7 per year, actually due to the 46.6 percent fetal hemoglobin being produced due to CTX-one treatment, which is far more than our primary endpoint target of 20%. Overall, while early, these data demonstrate that CTX-one is a promising approach to treating these severe hemoglobinopathy. I will now turn the call back to Sam.
Thank you, Tony. We and our pharmaceuticals are very encouraged by this first set of clinical data for our CTX-one program. While these data are early, they show that this could be a one time curative therapy for patients suffering from sickle cell disease and pain. This is a major landmark for CRISPR and highlights the potential for gene editing to provide cures for serious diseases. We would like to acknowledge our colleagues at Vertex Pharmaceuticals for their close attention.
And above all, we would like to thank the patients, their families and the investigators who have had the courage to participate in this groundbreaking clinical research. We will now turn to your questions. Operator?
Certainly. We will take our first question from course
of the reported SAEs? And like how can you just walk us through the time course of the reported SAEs and how long after the preconditioning treatment was the sepsis reported in the sickle cell disease patient? And even if these events occurred prior to transfusion of CTX-one? And I have a follow-up.
Thanks for the question. I think overall, the safety profile that's observed in both the thalassemia and sickle studies have been consistent with what you expect for an autologous stem cell transplant, and none of the serious adverse events were considered related to Tier 1. And the more important point broadly is from a risk benefit standpoint, given the tremendous benefits that these therapies offer, there's significant enthusiasm with the risk that you have with autologous transplants. I'll also ask Tony Ho, our Head of R and D to make comments and answer questions on the
Yes. The AEs we observed is typical of Fusilfin conditioning and we're working with centers that will manage these side effects.
Great. And then, do you guys have any data here on the proportion of biallelic editing that you guys observed? And the percent of RBHVF, is this correlated with increasing the lifespan of the RBCs?
Yes. It's a good question. I think we do measure as we dose these patients, we have to measure the editing rates in the drug product, but also in the periphery over time course. At this point, we have not disclosed the allelic editing rate, But I think what's very encouraging is the level of or nearly all of the cells have fetal hemoglobin in there. And the pan cellular expression of fetal hemoglobin is very important for disease amelioration from a pathophysiology stand point and that is a very high number in terms of the F cell.
Our next question will come from Ted Tenthoff with Piper Jaffray. Please go ahead.
Great. Thank you. Question on patient numbers. Why 2 and maybe you can give us a sense of additional enrollment where it stands in the two studies? Thanks.
Thank you, Seth, for the question. There have been significant enthusiasm for the studies and we have enrolled a number of patients in both studies and actually manufactured drug products for a number of patients. At this point, we have data thing to do to release the data now for 1 patient each in each of these trials. We're quite excited by the data. Few months and a year, we expect to enroll rapidly and dose patients rapidly to get to a reasonable cohort in each of these trials and look forward to a medical conference next year.
Our next question comes from Maury Raycroft with Jefferies.
Hi, everyone. Good morning and congrats on the update today. Thanks for taking my questions too. So just wondering if you can contextualize these patients' baseline characteristics, including their VOC and transfusion needs and potentially how this compares to what we've seen with competitor programs?
Thank you. I think both of these patients that are that have been dosed with CTX-one had a serious disease in the thalassemia trial, the patient transfusion burden prior to coming into the trial, nearly 16 transfusions per year on an annualized basis. And the mutation that we look at non beta-zero, it's a beta-zero IVSI-one hundred and ten mutation, which means that they had very low baseline globin, beta globin that's being produced. Even in this patient with severe disease burden, we saw in terms of fetal hemoglobin being produced and we see nearly 10 grams per deciliter of fetal hemoglobin and a total hemoglobin level that's above 11. I think that's very encouraging for us to see in a patient in thalassemia that's suffering from a serious disease type that we've treated.
We obviously disclosed earlier that we have now expanded the trial to beta 0 patients and look for patients into the CLIMB-one hundred and eleven trial. On the sickle cell disease side, the patient again came in with significant disease burden with a number of VOCs, at least 7 VOCs per year on an annualized basis before coming into the study. And for this patient, what we see while the data are early at the 4 month mark, we see that there is a a significant proportion of fetal hemoglobin important ratio to understand in the sense that fetal hemoglobin acts like as an anti sickling globin and with 46% fetal hemoglobin, you're seeing a very high proportion of anti sickling globin cells and a high pantilularity. We've also seen that the patient has not had any VOCs since being infused with CTX-one, which is a very encouraging sign. We obviously hope to follow-up on these patients for an extended period of time point.
What we see gives us is very encouraging and has the promise of providing a one time functional cure for these patients.
Our next question will come from Silvan Turkian with Oppenheimer. Please go ahead.
Thank you. Congrats on this very early data set and thanks for taking my question. I just want to know in terms of continued trial execution, are there any more DSMB hurdles that you internally have before you dose next patients or several patients? I
think the way the trials are designed, I think in each of these trials, the idea is to dose the first two patients serially. And once you make sure that these patients have safely engrafted with their drug product, then you can open up for a parallel number of sites. We hope to get to that point soon after dosing 2 patients in each trial and then expanding in parallel across a number of sites that are all excited about this trial and are well qualified to undertake a trial like this such as this. Great.
And then could you please quantify the baseline hemoglobin total hemoglobin levels of these patients? Were they kind of in line with the typical patient or not?
Allcemia context of the baseline hemoglobin, it's a tricky one to say what the number is because they get continuous transfusions. So what you're seeing in the baseline level of hemoglobin is the RBCs from the transfused blood. What we do know is that for the genotype that we've seen here, which is a beta0IVSI 110 genotype, they're producing very low baseline beta globin. They essentially behave like a beta0 patient. And in that context, I think what we see in terms of the fetal hemoglobin being produced from our 1 drug is quite encouraging and the fact that every leader at a and sort of holds steady is also very points to a durable effect.
So I think it's that's a harder one to quantitate. I think on sickle cell, again, you do produce on a baseline level a lot of sickling globa S that's being produced. But I think what we see is what's important from a disease mechanism standpoint is the ratio again of the sickling to anti sickling globin. And at this point, we're anti sickling globin or fetal hemoglobin than the endogenous sickling globin.
Our next question will come from Gena Wang with Barclays.
Please go ahead. Thank you for taking my questions. First, I wanted to congratulate you on the data. Really impressive. So the first question is, Sam, regarding the editing efficiency, it is fair to say that it's still consistent with what we have seen so far with cell line system, which usually is over 90%?
Yes. I think thank you, Gina. We're obviously very pleased and excited about the data. We've cleared the editing rates. And we'll continue to measure for all the drug products we make and then we'll also measure the editing rate that you observe in the periphery as well as the bone marrow and we look forward to the with what we've shown with our preclinical data before we filed our IND and our CTA application.
So platform is very facile and allows for an easy scale up into manufacturing and you continue to see those sort of consistencies at a patient scale on those manufacturing processes over time to make it even better than what we've seen in the past. But as we have more experience with patients, we continue to apply those lessons into our process development and manufacturing.
Next question from Ravi Ramotra with Evercore ISI. Please go ahead.
Hey, thanks for taking my question. Sam, it was surprising. I'm going to ask you a pretty big picture question. Congrats on this in the ex vivo editing setting. Just take us through your thoughts on the transferability of today's data to other settings.
Thank you, Ravi. And as I opened the remarks I said, which are moment for us not just for the hemoglobinopathies program, but for the rest of our portfolio as well. I think if you think about our portfolio at CRISPR Therapeutics, we've actually it's been a learning from the CTX-one product in terms of a simple edit and doing ex vivo editing in an autologous setting to then transfer that and learn from that into our immuno oncology products where we have more complex edits setting and beyond that into Regen Med where we have a program against type 1 diabetes where we have even more complex edits. So I think these early data, obviously, tremendous promise for hemoglobinopathies, but they in some ways foreshadow what we're trying to see and expect to see with our immuno oncology and our REGEN Med products as well in terms of the manufacture ability and ultimately the ability to dose these safely in patients. So we are quite excited for the rest of the ex vivo portfolio as well.
And overall, I think it does say that this heralds the coming of gene editing and a new type of therapy into medicine, which would apply into in vivo as well in the long run.
Got it. Thank you. Congrats, Ken.
Great. Thank you.
This does conclude today's program. Thank you for your participation. You may now disconnect.