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spk03: Thank you all for standing by and welcome to the Sangamo Third Quarter 2021 teleconference call. All participants are in a listen-only mode until the question and answer session of today's conference. To ask a question over the phone by that time, you may press the star key followed by the number one. Please also note that today's call is being recorded. I'll now turn the call over to your host, Aaron Feingold, Head of Corporate Communications. Ma'am, you may now begin.
spk16: Good morning, and thank you for joining us today. With me this morning on this call are several members of the Sangamo Executive Leadership Team, including Sandy McRae, Chief Executive Officer, Mark McClung, Chief Operating Officer, Pratusha Durrababu, Chief Financial Officer, Jason Fontenot, Chief Scientific Officer, Rob Schott, Head of Development, and Bettina Cockroft, Chief Medical Officer. Slides from our corporate presentation can be found on our website, sangamo.com, under the Investors and Media section under the Events and Presentations page. This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements relating to therapeutic and commercial potential of our product candidates. The anticipated plans and timelines of Sangamo and our collaborators for conducting clinical trials and presenting clinical data, execution of our corporate strategy, advancement of our product candidates, our revised 2021 financial guidance, and other statements that are not historical facts. Actual results may differ materially from what we discussed today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC Specifically, our annual report on Form 10-K for the fiscal year ended December 31, 2020, as supplemented by our quarterly report on Form 10-Q for the fiscal quarter ended September 30, 2021. The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information except as required by law. On this call, we discuss our non-GAAP operating expenses. Reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website. Now, I'd like to turn the call over to our CEO, Sandy McRae.
spk09: Thank you, Aaron, and good morning to everyone on the call. This is such an important moment for Sangamo, as we share clinical data and business updates across several programs, demonstrating that we have three important assets in or progressing towards late-stage development. Our gene therapy portfolio is advancing with accumulating safety and efficacy data in our Fabry and Haemophilia A programs. Additionally, we are delighted with the preliminary proof of concept data demonstrating the clinical potential of our genome engineering zinc finger technology in sickle cell disease. This morning, we announced preliminary clinical data from our phase one two-star study, evaluating Isoralgagene, Sivoparvivec, or ST920, our Fabry disease gene therapy product candidate. Data from this important study were evaluated from the four patients in the first two cohorts, those levels 0.5E13 and 1E13 BG per TIG. As of the cutoff date, September 17th of this year, These encouraging results showed that for the first four patients, ST920 was generally well tolerated. There were no treatment-related adverse events higher than grade one and no treatment-related serious adverse events. No patients experienced liver enzyme elevations or required steroid treatment. All four patients exhibited above normal alpha-gallate activity. which were maintained for up to one year for the first patient treated and through 14 weeks for the most recently treated patients. Levels ranged from 2 to 15-fold above normal levels at last measurement as of the cut-off date. Interestingly, the first three patients still reported improvements in ability to sweat, a primary and common Fabry disease symptom that limits exercise tolerance for the patient. ERT withdrawal is now complete for one patient and is planned for the other patient on ERT, based on the stability of their alpha-galli activity following treatment. Based on these data, we have initiated phase 3 planning. The fifth patient in the study, who is the first patient in the third dose cohort at 3E13, was recently dosed. The sixth patient is currently in screening, also for the third dose cohort. and we expect to provide updated results throughout 2022 and present these data at a medical meeting. This morning, we also announced that preliminary proof-of-concept results from the Phase 1-2 precision study of SAR 445136 and investigational zinc finger nucleus gene-edited cell therapy in patients with sickle cell disease will be presented at ASH. This program is partnered with our friends at Sanofi. The data in the abstract shows that as of June 25th, 2021 cutoff date, none of the four patients treated required blood transfusions, post-engraftment through 65 weeks of follow-up for the longest treated patients. The four treated patients all experienced increases in total hemoglobin, fetal hemoglobin, and percent F cells. No adverse events or serious adverse events related to treatment were reported as of the cutoff date. Further data will be provided in a poster presentation at ASH on December the 12th. Sangamo and Sanofi are continuing to advance the sickle cell disease program. The company's recently obtained manufacturing requirements guidance from the FDA in preparation for potential further clinical studies. Separately, we in Sanofi made the business decision to cease development for the beta thalassemia indication and allowing us to focus resources on the sickle cell disease program. Moving now on to our haemophilia aid program partnered with Pfizer, we announced this morning the updated follow-up results from the Phase 1-2 ALTA study of durotocogene phytocarvavec will be presented at ASH. For the four patients in the highest dose cohort who have been followed for at least 104 weeks as of May 19, 2021 cutoff, mean factor rate activity was 30.9% at week 104 as measured by chromogenic assay. In this cohort, annualized bleeding rate was zero for the first year after treatment and 0.9 throughout total duration of follow-up. As demonstrated in this study, the gene therapy was generally well tolerated in patients with severe haemophilia A. Further data will be provided in a poster presentation at ASH on December the 12th, 2021. We and Pfizer also announced that some of the patients treated to date in the phase three of fine trial experienced factor VIII levels greater than 150% following treatment. To date, none of these patients have experienced thrombotic events, and some have been treated with direct oral anticoagulants to reduce thrombotic risk. Out of an abundance of caution, Pfizer voluntary paused screening and dosing of patients in the trial in order to implement a protocol amendment which will provide guidelines for clinical management of elevated factor VIII levels. On November 3, Pfizer was informed that the FDA has put this trial on clinical hold. Pfizer and Sangamo are committed to resuming patient dosing as soon as possible. We continue to believe that this gene therapy will represent an important treatment option for patients with haemophilia A. The next step is to share the proposed protocol amendment with health authorities and respond to the clinical hold, after which the companies will be able to provide updated timing for the trial. Turning now to our kidney transplant programme, we have now enrolled the first patient in our Phase 1-2 Steadfast Study, evaluating TX200, our wholly-owned autologous CAR Treg cell therapy candidate. We believe that this is the first in-human CAR Treg study and that this field is growing with much excitement as a promising approach for challenging autoimmune conditions. In this study, similar to other genetically engineered cell therapy approaches, patients will undergo a lookup procedure from which their Treg cells will be isolated, engineered, and then cryopreserved. The HLA-A2 negative patient will subsequently undergo kidney transplant and, following a recovery period, will receive their personalized TX200 therapy. We expect to dose the first two patients in this study by the middle of 2022, following their kidney transplants. We continue to open sites and screen patients. We believe this proof of concept study may represent an important treatment for patients undergoing renal transplant and will help us understand CAR Treg biology in humans, as well as advanced process development knowledge. We hope that this study establishes the foundation for a portfolio of wholly owned CAR Treg therapies for autoimmune indications. Finally, I'm delighted to share that Mark McClung has been appointed as Sangamo's Chief Operating Officer effective November 1st. Mark's expanded role as COO is an important organisational step for Sangamo, which will support the multiple advancing wholly owned and partnered programmes. We look forward to Mark's continued leadership as we continue to build the capabilities to bring genomic medicines to patients and to the marketplace. Everyone at Sangamo is thrilled about this clinical momentum, and we look forward to presenting updated Fabry results throughout 2022, as well as working with our collaboration partners and investigators to present the ASH data in December. And with that, I'll turn the call over to Patricia for a financial update. Patricia.
spk10: Thank you, Sandy, and good morning. Our financial results for this quarter are available in the press release issued this morning, which can also be found on our website. I want to reiterate that this is an exciting moment for us as a company. And this quarter, we continue to invest in the advancement of our clinical programs, including Febreed and TX200, our preclinical research pipeline, and our in-house manufacturing capabilities. With approximately $519 million in cash, cash equivalents, and marketable securities at the end of the quarter, we believe that our balance sheet remains strong. Turning to 2021 full-year guidance, We expect non-GAAP operating expenses to be between $265 million to $275 million for the year, which is within the range of the guidance that we have previously provided. This range excludes estimated non-cash stock-based compensation expense of approximately $35 million. I will now turn the call back to Sandy for closing remarks.
spk09: Thank you, Patricia. We are very excited by today's clinical data readouts, which show the advancement of our first-generation genomic medicine pipeline with traditional gene therapy and autologous cell therapy. These programs potentially pave the way for our next-generation focus on genome regulation and allogeneic CAR-T reg cell therapy, where we have a robust preclinical pipeline in neurological and autoimmune diseases, respectively. We're delighted with the positive momentum and look forward to updating you in the near term about several potential catalysts, including presentation at ASH of four-patient sickle cell disease Phase 1-2 data, presentation at ASH of two-year Phase 1-2 haemophilia data, and additionally, we'll provide a timing update for the Phase 3 trial once the proposed protocol amendment and response to the hold is shared with health authorities. Dosing of the six patients and updated Fabry Phase 1-2 data presentations throughout 2022, including at a medical meeting. Dosing of the first two patients in the Steadfast Phase 1-2 study by the middle of 2022. And completion of our in-house cell therapy manufacturing facility in our Valbonne, France location, following the completion of our in-house manufacturing facility in our Brisbane, California headquarters this past quarter. So we'll now turn it over to the operator to open the line for questions.
spk03: Thank you, speakers. Participants will now begin the question and answer session. As a reminder, to ask a question over the phone, you may press the star key followed by the number one. To withdraw your request, you may press the pound key. Again, that's star one to ask a question or the pound key to withdraw your request. Speakers, first question is from the line of Aspen Morey of Bank of America. Your line is now open.
spk04: Hey, guys. Thanks for the question. So on Fabry, I think you previously hadn't expected to share some enzyme replacement therapy withdrawal data in this year-end release. It's good to see that the time frame seems to maybe have been faster than expected. But with that in mind, I guess, is there any patterns you're seeing in the time frame it takes from getting from a from the dose of ST920 to removal of that therapy. And it also appears that maybe the patient four kind of got to that milestone a little quicker than patient one who had a longer follow-up. Just wanted to see if there's anything you're seeing there to explain that. Thank you.
spk09: So thank you for your question. I think what I'm hearing you're asking about is about ERT withdrawal. So, we thought it was important to truly understand the effect duration, and we've been very pleased that over the course of a year in the longest treated patients, there's been a consistency of effect. And we then have discussions with the investigators, and at the appropriate point for them and for their patient, they will withdraw treatment. And the first patient was only withdrawn very recently, and the second one is planned to be withdrawn this year. And so we will share that data at an appropriate time. Okay, thanks.
spk04: And then I have one more on Fabry. Are there any trends you're seeing among patients one and four that signal maybe what's driving better alpha-GalA response than you're seeing with patients two and three? I think two and three might have had lower baseline GB3, but if there's anything you can point to that would help out there.
spk09: Well, so there's only four patients, so it's very difficult to say anything specific. It is Notable, though, that patients 1 and 4 are on ERT and patients 2 and 3 are not. And it may be that there is some additional effect from the ERT that is leading to that effect. But I think that is only speculation, and we need to dose more patients to understand it. Okay. Thanks, Andy. Appreciate it.
spk03: Next question is from Yanan Zhu of Wells Fargo. Your line's now open.
spk13: Hi, thanks for taking my questions. I have a question on Fabry and maybe also additional questions on other updates. But Fabry, could you, Sandy, comment on the dose response here? And also, I think for patient two, there was an increase in enzyme levels above normal, but the substrate levels seemed to be flat. So could you shed some light on that finding? Thanks.
spk09: It's a good question, and I think this has been something that's been consistently seen across all of the research into Fabry disease. If the substrate levels are low, they don't change in the treatment period. But Bettina, do you have thoughts on this, on the dose response that we've seen?
spk01: Thank you, Sandy. So as Sandy mentioned, we have now dosed two patients in cohort one and two patients in cohort two. This is still a small sample size. This needs to be emphasized at this point in time. But Regarding the levels of lyso-GB3, for sure, in three of the four patients, those lyso-GB3 levels started off low, and as Sandy mentioned, across programs, it has been seen that these remain stable if they are low to start with. If you look at patient three, this patient's lyso-GB3 levels start off high, and the levels of lyso-GB3 were reduced by about 40% within 10 weeks after dosing. And this reduction was maintained through 32 weeks. So at this point in time with such a small sample size, it is really difficult to talk about those relationships. I would say that throughout 2022, we anticipate to share more data. And that data will also be shared at a medical meeting. So there will be more granularity and data to come.
spk09: But what I want you to take away is how excited we are by this because all four patients are above the normal physiological level. All four patients have shown consistency of response in the time that they've been observed. Three of the four patients are already reporting patient effects that are very encouraging about the effect of the drug. And we are already into the next higher cohort. And as Bettina says, We'll talk about this next year.
spk13: Great, thanks. And on the clinical hold for the hemophilia A, collaborated hemophilia A program, I was wondering how high is the factor VIII level? I thought we had seen like 200% from other studies. So could you shed some light on the rationale for that clinical hold? And lastly, a question on BIVV003, a very quick one that is at ASH, would we see VOC data for the treated patients? Thank you.
spk09: So I'm going to pass the question on hemophilia to Rob. Rob, can you talk to this?
spk08: Yeah, we have seen elevations of factor VIII greater than 150% in some patients. This is an ongoing phase three trial, so we're not getting very specific with the data. around this. There were no venous thromboembolic events associated with these elevated levels, and the decision to voluntarily pause the trial was out of an abundance of caution. And as anticipated, the FDA followed through with a clinical hold that was, we were notified of that late yesterday. It's our plan to with Pfizer to submit a protocol amendment and have a discussion with the agency and resume the trial when it is appropriate to do so.
spk09: And regarding sickle cell disease, we'll show the full data set at ASH in December.
spk13: Great. Thanks for the update.
spk03: Thank you. Next question is from Luca Isi of RBC Capital. Your line's now open.
spk11: Well, great. Thanks so much for taking my question. Congrats on all the progress. Maybe on Fabry disease, exciting early proof of concept. I'm wondering if you can comment on how you're thinking about the Phase III study design. On hemophilia A, maybe if you can provide any additional color on the protocol amendment that you're thinking about to minimize the risk going forward. And then maybe on Base 1000, can you just expand a little bit more on the rationale behind the decision to terminate a program? Thanks so much.
spk09: Goodness. So it's so exciting to be talking about base redesign. because we are very pleased with the results. But we need to see the results of the third cohort to really be able to understand which dose we're taking forward and how we design the study. But I can reassure you that planning and the full... energy behind a phase three has already started on these programs. Let me then pass the hemophilia question to Rob and the beta thalassemia one tomorrow.
spk08: Yes, with regard to the protocol amendment, we're not disclosing any of the specifics of the protocol amendment at this time, but the protocol amendment is being considered and will be submitted promptly and in discussion with the agency in response to the clinical.
spk09: And the current plan is to find the best way to guide management of any patient that has a higher level.
spk08: Yes, there'll be monitoring and management of the patients with levels of factor VIII that are greater than 150%.
spk09: But we feel it important to restate every time that conversation comes up that no patient has come to harm. There have been no adverse events related to this. And this is an abundance of caution, and I think a correct abundance of caution, because this is a gene therapy that we need to take very seriously and do the best for the patients.
spk14: Mark? Yeah, so in terms of the beta-foul decision, it was really a business decision that we took alongside our partners at Sanofi. just due to the timing and relative to where the competitive set lies in terms of their development. We felt that it is important to really focus our effort and our resources solely on sickle cell disease.
spk09: And drive forward together.
spk11: Got it. Thanks so much, guys.
spk03: Next question is from Maury Raycroft of Jefferies. Your line is now open.
spk06: Hi, everyone. Good morning, and congrats on the update today. For Fabry, just wondering if you can talk more about the alpha-gal data being 2 to 15-fold higher than normal. It seems higher than competitor data at month 12 that showed about 5 to 6-fold higher. I guess what's the best way to contextualize your data versus competitors, and how could this translate to kidney substrate reduction? Thank you, Maury. Bettina, do you want to talk about Fabry?
spk01: Sure. Thank you, Sandy. So in terms of the alpha-gal data, we're obviously very excited to see the superphysiologic alpha-gal expression that we are seeing with all four patients. I think at this point, it is early to compare and probably not the right place to do comparisons across programs. We look forward to sharing more granularity on this data at an upcoming meeting in 2022. So that also goes to any additional data related to kidney substrate.
spk09: You can imagine though that having seen efficacy at the two initial cohorts and moving into a third higher cohort, it gives us enormous that this is going to be a medicine that will be useful for patients with FAPRI. It really is compelling data. Early as it is, we find it compelling data.
spk08: And I would add that a priori, we had targeted superphysiologic expressions of alpha-gal-A and plasma to drive clearance from tissues. So this is a desired effect, what we're seeing.
spk06: Got it. It's all helpful. And maybe just one follow-up. If you can compare and contrast the Fabry observations and gene expression and dose with your hemophilia gene therapy program, maybe if you can talk more about that.
spk09: That's a good question. We are fortunate that we've used ATV6 now in several programs and we understand the safety of it and across all of the programs we've had very few adverse events. In addition, if you look at the point at which there's an inflection of efficacy, it's about the 1 to 3 E13 in haemophilia and it's even earlier than that in the Fabry disease program. Other than that, we're very pleased with the safety and efficacy we've now seen in our two gene therapy programs.
spk06: Got it. Okay, thanks for taking my questions. Congrats again.
spk03: Next question is from Nicole Germino, Truva Securities. Your line is now open.
spk15: Good morning. Thanks for taking my questions, and congrats on the progress. So I dialed in a little bit late and I might have missed some of the opening remarks, so I apologize if my questions are already addressed. But for Fabre, can you talk about how the primary symptoms have improved over time from baseline and any color on cardiac function? And for Hime, how long from infusion did these excursions happen and how often are factor VIII levels being assessed going forward to monitor?
spk09: So your line is a little unclear. So let me read back to see that I understood your question. It's about the patient symptoms in Fabry, and it's about how we manage the patients in hemophilia. Is that correct? Yes.
spk15: And for hemophilia, how long from the infusion did these surgeons happen?
spk09: So Bettina, can you say what we know about the patient-reported symptoms in Fabry, please?
spk01: Yes, of course. So as a reminder, again, I'd like to emphasize this is early data that we're sharing, early preliminary data. The patients in course one, two, three of the four patients had anhydrosis reported at baseline. And some of these patients, these three patients have reported improvement in sweating or perspiration, which is a favorable outcome for patients in the time period over the course of the study that we have seen so far. One of the patients also had seen stabilization of cardiac structure on serial assessments on imaging. So these are preliminary reports that we are gathering, and as I mentioned before, we will be sharing more information over the course of next year of some of these details.
spk08: I'd like to add that if you look at the totality of the data, including the patient's observations that were relayed to the investigators, the alpha-gal expression, the adverse events, that all of the data are all pointing in a favorable direction. So we would like you to look at the data in its totality, not just each individual component.
spk15: Great. And then for Hime, how long from the infusion did the excursions happen?
spk08: This is an ongoing phase three trial, so we aren't disclosing the specifics around the data. we want to keep that phase three trial protected because it's a potential registration trial.
spk15: Great, thanks.
spk03: Next question is from Gina Wang of Barclays. Your line is now open.
spk07: This is Tom for Gina. Thanks for taking the question. So for the Fabry, just one question with the dosing and the alpha-gal enzyme level. Do you plan to dose higher depending on the data radar? And what is your ultimate goal of that alpha-gal level in the serum? Is the current super physiological level enough in your thought? And how about the alpha-gal enzyme level change after the patient who withdraws from the ERT? Great question.
spk09: Well, can we do Fabry first? So we make sure we cover all your questions. We've never said it must be this for alpha-gal, because this is the first time that people have really done gene therapy in Fabry disease. And so there isn't a definitive level we've always thought it had to be better than normal physiological levels. And we're pleased that the patients both on ERT and off ERT are at that level. And now what we're doing is withdrawing the ERT and seeing where the levels provided by the gene therapy in the liver level out. And until we do that experiment, we really won't understand this fully. Okay. We are also dosing at 3E13, which is three times higher than the current dose. And once we see that data in its totality, we will be able to decide which dose to take forward into phase three. But we felt that the first two cohorts were so compelling, as Rob says, with the alpha-gal, with the patient safety, with the patient-related outcomes that came spontaneously from patients talking to the investigator about things that are important to them, like ability to exercise because they can now sweat, that we felt that this data was exciting and compelling and wanted to share it with the broader community.
spk07: Okay, great. That's very helpful. And maybe just a quick follow up on the February that you comment that you will share additional data, including the clinic function data in the 2022 medical meeting. And will that be include like kidney inclusion or it will be EGFR? like the filtration function measurement? Can you help us to set an expectation for that?
spk09: It's unlikely that we'll be sharing renal biopsy data in 2022. The patient would undergo an initial biopsy and then some months later, a second one. So that data is unlikely to be available in 2022. Okay.
spk07: Okay, thanks for that. And for the HEMO-A, so we know that there will be protocol amendment. Other than that, do you expect any additional steps that are required in order to remove the clinical hold? Or the implementation of the oral anticoagulant will be the only one that would be required?
spk09: I have enormous confidence in our colleagues at Pfizer. They're putting together an amendment that puts patients first. and make sure that the patient always remains safe, and then they will discuss that and present it to the agency, and hopefully we'll be able to move forward with this trial. As Pfizer have said, over 50% of the patients have been enrolled now, and they had a pre-study study to collect the patients to have them ready to go into the trial. So we think this will move forward and are sure that Pfizer is doing the right thing.
spk07: Okay. Thanks for that.
spk03: Next question is from Rita Baral of Cohen. Your line is now open.
spk02: Hi, guys. Thanks for taking the question. As part of this phase one, two, what other clinical, I guess, a clinical quality of life or patient-reported symptomatology are you capturing? Sandy, you mentioned improvement in sweating. Are there other things that are being proactively asked clinical symptomatology-wise? And then can you talk at all about sort of the curve of expression that you're Like for patient one, that 15-fold at week 52, can you confirm that that's like the top expression that you've seen? And for patient four, that you're sort of continuing on your way up and anything you can say about the curves?
spk09: Okay, so we measure a whole slew of things, including formal patient-related outcomes. We want to be very clear, this was spontaneous, patients spontaneously talking to their investigator to tell them of the changes that they've known, and the investigator felt compelled to tell us because it was important. We will measure... This going on in the phase three and because it's not just about the enzyme, what's important is what's important to the patient. And it's things like the neuropathic like pain that they have. It's about the sweating. It's about the quality of their life and their energy. And so we want to capture all these things. The second question I think that you're asking is about duration. That's very pleasing to us because this is a solution we want for as long as possible for those patients. And in all of the patients, once it gets to its plateau level, it has remained at that level throughout the duration of the study. And we will continue to follow these patients and report hopefully the continued duration of effect.
spk02: Got it. And just given the change in, I guess, the regulatory landscape in FABRI over the last 12 months or so, are there any plans to potentially add biopsy to this study, or is that going to be reserved for the next study? Kidney biopsy, I mean.
spk09: We have plans for biopsy in this study. It's just that the results will not be available within the 2022 phase. We've always said that we would not do the biopsy in the initial patients until we saw that the medicine was effective. And now we see the medicines effective biopsies will be part of the routine of the study.
spk02: Oh, got it. Okay. So maybe not these biopsy from these patients, but maybe the fifth and sixth patient with the highest dose. Is that the plan?
spk09: So the first four patients did not have renal biopsy, and future patients will as part of the study protocol.
spk02: Got it. Thanks for taking the questions.
spk09: Our pleasure.
spk03: Next question is from Ben Burnett of Steeple. Your line is now open.
spk05: Hey, thank you very much. I will echo my congratulations on the Fabry disease data. I did want to ask a couple questions around this. The first one, I would also agree with some of the others on the call. It seems like the enzyme activity is quite good, at least relative to competitors. But I guess just curious that the impact on lyso-GB3 just wasn't more profound, specifically on patients 1, 2, and 4. I guess how... What is your interpretation of those data, and how representative is lyso-GB3 in the plasma to what's happening inside of cells?
spk09: Good question. And until we biopsy, we won't have that direct correlation. I'll say again, in all of the Fabry trials from each of our competitors and us, patients who have low Lysol GB3 don't go lower. If it's already very low, it's hard to make it go lower. And that's across all of the trials. And yet, even in the trials that have done GB3, even in the Abrobio trial, for example, who showed a reduction in GB3 in the kidney, they also showed that effect, that it had to be a high lyso-GV3 to show a reduction in the plasma. It's a very different system that we're producing here, and we think this is what patients want. They want a one-time injection that is safe, that is effective at producing alpha-gal, and is effective at producing it over a long period of time, and that they notice a benefit, and we're already having indications that that's what's seen. Now we need to go to the next higher dose and hopefully show even more benefit and then pull all that data together and decide on the full design of this study for phase three and get this medicine to patients as soon as possible. But we are very pleased with the safety, the efficacy, the consistency, and the patient benefit that we've seen so far.
spk05: Understood. Okay, that's helpful. And if I could just ask one sort of clarifying question on patient four. alpha-galactivity at week 14, you show an assessment that looks, I think, really good, but was this assessment made after they were weaned off of enzyme replacement therapy, or was that prior to that? Bettina, can you clarify, please?
spk01: Absolutely. So, patient number four has only been withdrawn from ERT therapy very recently, and after the cutoff data for what you're seeing on these slides that we have posted on our corporate website. So the data you're seeing is with the patient still on ERT. And just to clarify, all the data points are at truss ERT level. So dosing was prior to the ERT infusion. So the ERT withdrawal will have been after this data cut.
spk09: Okay. It's part of the reason that this therapy is, I think, offers a better solution than ERT. ERT has a very rapid C-max, and then it declines quickly. But we wanted to be particularly careful, and therefore we measured the trough level, usually about day 14 after the ERT, at the very last point before the patient had their next dose of ERT, to make sure there was no residual enzyme in the plasma. And that's something I think we all, in all the different studies from all the different companies, need to be careful about is making sure that the trough is the trough.
spk05: I understand. That makes sense. Okay. All right. Thank you very much for the call. Thank you.
spk03: Speakers, we have time for one more question from Andreas Argrides of Wedbush Securities. Your line is now open.
spk12: Good morning, and thank you for taking our questions. Let me also reiterate our congrats on this early encouraging data. Yeah, so for Fabry, just a quick one on the preexisting antibodies and your thoughts around any potential impact that may have. And then on the hemophilia A, does the protocol amendment restart the timeline for the ABR data. Thank you.
spk09: So let me answer the second one, then pass the antibodies to Bettina. Why this had to be treated seriously was these are patients in gene therapy, so when they get the medicine, it stays in their body even if the trial is paused. And so we and Pfizer will continue to collect data from the patients, even though the recruitment into it is paused. There's still information about prolongation of effect and safety of the medicine being collected by Pfizer. So it's unusual compared to a paused trial where the patient stops taking the medicine. The medicine is still there and continuing to have benefit for the patient, we hope. Bettina, the antibodies.
spk01: Yes, for the antibodies. So I think what is important to emphasize is this is early data on four patients. And it is early to make inferences as to whether antibodies and to what degree antibodies are having an effect on these patients. We need to bear in mind that two of these patients are on ERT, two are not. There is a lot of variability in the data at this point in time. So We look forward to seeing more data coming out from our next cohort, cohort three, and being able to assess that impact in a better manner.
spk09: But we haven't seen anything, any correlation up to now?
spk01: At this point in time, that would be difficult to say.
spk12: Sure. Okay. Understandable. Thank you for taking our questions. And again, congrats on encouraging data. Thanks.
spk03: Thank you, participants. I'll now turn the call back over to Erin Feingold for closing remarks.
spk16: Thank you once again for joining us today and for your questions. We look forward to keeping you updated on our future developments.
spk03: That concludes today's conference call. Thank you all for joining. You may now disconnect.
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