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spk17: The conference will begin shortly. To raise your hand during Q&A, you can dial star 1 1.
spk07: Ladies and gentlemen, thank you for standing by and welcome to Sangamo's second quarter 2022 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you need to press star 1-1. I would now like to turn the call over to your host, Louise Wilkie. You may begin.
spk12: Good afternoon.
spk01: I'm Louise Wilkie, Sangamo's Vice President in Investor Relations and Corporate Communications. Thank you for joining us on the call today. On this call are several members of the Sangamo Executive Leadership Team, including Sandy McRae, Chief Executive Officer, Mark McClung, Chief Operating Officer, Pratusha Durabibu, Chief Financial Officer, Jason Fontenot, Chief Scientific Officer, Rob Schott, Head of Development, and Bettina Cockcroft, Chief Medical Officer. Slides from our corporate presentation can be found at our website, sangamo.com, under the Investors and Media section of 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 the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for initiating and conducting clinical trials, dosing and screening of patients, and presenting clinical data, execution of our corporate and funding strategy, advancement of our product candidates, advancement of preclinical programs to the clinics, the sufficiency of our resources, our 2022 financial guidance, key milestones and catalysts, 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, but they're discussed in our filings with the SEC, specifically in our annual report on Form 10-K for the fiscal year ended December 31st, 2021, as supplemented by our quarterly report on Form 10-Q for the fiscal quarter ended June 30th, 2022. 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, Andy McRae.
spk11: Thank you, Louise, and good afternoon to everyone on the call. Sanger will continue to advance our mission to create potentially transformative genomic medicines for patients using our innovative technologies in the second quarter of 2022, with momentum across our clinical stage programs as well as significant preclinical progress. This quarter, we received endorsement from the Fabry Phase 1-2 Studies Safety Monitoring Committee to advance our differentiated and wholly owned gene therapy program for the treatment of adults with Fabry disease from the dose escalation phase into the expansion phase. We already have multiple patients in screening and expect to dose two patients later this month. We continue to be pleased with the progress of this important program and look forward to sharing updated patient data later this quarter. BIVV003, formerly known as SAR445136, Our zinc finger nucleus modified autologous cell therapy for the treatment of sickle cell disease formally completed the transition back to being a wholly owned sanguinal program on June 28, concluding our collaboration agreement with Sanofi. I'm really grateful for Sanofi's cooperation on the transition. We expect to dose the next patient in the phase 1-2 study in the third quarter of this year. I look forward to sharing an incremental data update in the second half of 2022. Momentum continued behind TX200, our wholly owned autologous CAR Treg cell therapy product candidate in HLA A2 mismatched kidney transplantation. Following the dosing of the first patient in March, in what we believe to have been the first in the CAR Treg cell therapy field, Most importantly, the patient remains well more than four months post transfusion. Manufacturing is complete for the second patient who received a kidney transplant in July and dosing is planned for later this quarter. I continue to be thankful to the investigators for helping us break ground in this potentially transformative field of cell therapy. Regarding the Phase III Haemophilia A gene therapy study, Pfizer advised us that it expects to resume dosing in a fine trial in the third quarter of 2022, with a pivotal readout estimated in late 23 or early 24. Finally, I was thrilled to attend and see the reaction to Sanger's most important contributions at the American Society of Gene and Cell Therapy, ASGCT, annual meeting in Washington, D.C. in May. We presented a total of eight posters and presentations detailing our highly innovative early stage science, which we see as essential to feeding our ongoing pipeline of genomic medicines. I'm proud with the versatility of our scientific platforms, coupled with the strategic and focused use of research and development capabilities, which are driving progress in our pursuit of indications of unmet need. I recognise the difficult market conditions, though, being experienced across the industry. We believe signing the most current financial position and the variety of options we have to raise further funds positions us well to continue developing new transformational medicines for patients in need and to generate long-term value for our shareholders. And with that, I'd like to turn the call over to our Head of Development, Rob Shaw, who will discuss the data from our clinical programmes in more detail. Rob.
spk14: Thank you, Sandy, and good afternoon to everyone on the call. The second quarter marked another period of strong execution in the clinic, and we are pleased with the progress across our programs. In the Phase 1-2 STAR study evaluating israldragine sitaparvovac, or SP920, our wholly-owned gene therapy program for the treatment of Febre disease in adults. Two additional patients were withdrawn from enzyme replacement therapy, or ERT. Out of the five patients that began the STAR study on ERT, a total of four have now been successfully taken off ERT, one each in cohorts one and two, and two in cohort three, with discussions in progress to withdraw the fifth and final patient from ERT. I'm pleased to report that all four withdrawn patients have stable biomarkers and an estimation of investigators have not required resumption of ERT. As Sandy mentioned, this quarter, the Safety Monitoring Committee for the STAR study endorsed progressing from the phase 1-2 escalation phase into the expansion phase at the 5E13 vector genome per kilogram dose level. We expect to dose two patients imminently and have multiple patients in screening, including both male and female candidates. A total of 16 study sites are now open and recruiting, including the first sites in Canada, Italy, and Australia. The safety and efficacy from the dose escalation phase has been closely followed by investigators, and interest in participation in the trial of this wholly-owned therapy is growing among the Fabry community, including, most importantly, with patients. We look forward to providing updated results from the Phase 1-2 STAR study during the second half of 2022, including at the Society for the Study of Inborn Errors of Metabolism, SSIEM, Annual Symposium, taking place at the end of August. We also continue to actively plan for potential phase three study and are engaging with health authorities, patient advocacy groups, and investigators. As Sandy mentioned, on June 28th, we assumed full control of BIVV003, formerly known as SAR445136, for the treatment of sickle cell disease, a promising program we're excited to have back as part of our wholly owned pipeline. In the Phase 1-2 Precision 1 study, three of the four patients dosed with product candidate manufactured using the previous manufacturing process continued to be free of vaso-occlusive events since dosing. During this quarter, the patient who had achieved the lowest level of fetal hemoglobin post-infusion experienced a second vaso-occlusive crisis. This patient has now fully recovered. During this quarter, manufacturing of product candidates using improved methods progressed in the Phase 1-2 study. These improved manufacturing methods have been shown in internal experiments to increase the number of long-term progenitor cells in the final product. We expect to dose the next patient in this study in the third quarter of this year and look forward to sharing an incremental Phase 1-2 data update before the end of the year. In addition, Phase 3 enabling activities, including manufacturing readiness, actively continue. Progress continued in the Phase 1-2 Steadfast Study, our groundbreaking, wholly-owned TX200 CAR Treg cell therapy candidate for the prevention of immune-mediated rejection in HLA A2 mismatched kidney transplantation from a living donor. Following our announcement in March that we had successfully dosed what we believe to have been the first-ever patient with an engineered CAR Treg, the product candidate dose continues to be well-tolerated more than four months post-infusion with no treatment-related adverse events. We are thrilled to report this important update as we believe it is a historic first. This quarter, we completed manufacturing for the second patient in the Steadfast study. This patient recently received a kidney transplant and is expected to be dosed later in the third quarter of 2022. We hope to dose the third and final patient in cohort one by the end of 2022 We plan to provide further updates once we have meaningful package of data to disclose from our first complete cohort. In addition, this quarter we are pleased to announce that the European Commission has granted orphan medicinal product designation to TX200 for the treatment in solid organ transplantation following a positive opinion from the European Medicines Agency Committee for Orphan Medicinal Products. To qualify for orphan designation, a treatment must be intended for a life-threatening or chronically debilitating disease affecting fewer than 5 and 10,000 people. Importantly, no satisfactory method of treatment must exist, or if such a method exists, the treatment must be of significant benefit to patients. The achievement of this important regulatory milestone takes us one step closer to our goal of creating a transformative therapy that can reduce the likelihood of organ rejection relieve the overall patient burden, and minimize the risks that come with immunosuppressive medications. As a reminder, this is the first in a pipeline of potential CAR Treg therapies that are working to develop to address a range of autoimmune conditions. In addition to TX200, Sangamo has an active preclinical pipeline with multiple candidates in development to treat inflammatory bowel disease and multiple sclerosis alongside our efforts to progress the allogeneic cell therapy platform. Finally, regarding the phase three of FINE trial evaluating Grotogen Sitalparvavec, an investigational gene therapy for hemophilia A, Pfizer advised us that it continues to expect to resume dosing this quarter once all necessary conditions are met, including approval of an updated trial protocols by regulatory authorities. Pfizer has provided guidance study Pivotal data readout is expected toward the end of 2023 or in early 2024. I will now turn the call over to our Chief Scientific Officer, Jason Fontenot, for updates on our preclinical research programs. Jason?
spk10: Thank you, Rob, and good afternoon, everyone. I'm very pleased to report that we continue to leverage Sangamo's cutting-edge genomic engineering and cell therapy platforms to advance both wholly owned and partnered programs toward the clinic. We are also making remarkable progress in expanding our proprietary genomic engineering toolkit and in developing novel AAV capsids to enable more effective, therapeutically relevant delivery of those tools. We shared a portion of this exciting progress at the ASGCT annual meeting in May, where Sangamo scientists presented seven poster presentations and one oral presentation, demonstrating advancements across our research portfolio and highlighting the diversity and versatility of our genomic engineering platform. Notably, two of the ASGCT presentations showcased our world-class AAV-casted evolution platform. The initial focus of this work is delivery to the central nervous system. We anticipate that more effective and efficient AAV-mediated delivery to the CNS will allow us to deploy our genomic medicines to an even larger set of high-value neurodegenerative and neurodevelopmental diseases. The ASGCT presentations highlighted significant and exciting progress in the development of engineered AAV capsids facilitating broad CNS coverage using both cerebral spinal fluid administration and intravenous administration. Regarding our genomic engineering platform, This year's ASTCT marked the unveiling of our compact and highly efficient zinc finger base editor and the deployment of our epigenetic zinc finger regulators to engineer T cells and other immune cell types. The zinc finger base editor can facilitate simultaneous inactivation of multiple genes without introducing double-stranded breaks, thus reducing the probability of chromosomal translocation events. A notable aspect of our base editor is its compact architecture. packaging into a single AAV vector. This is a critical requirement for the efficient use in many therapeutic applications, particularly in vivo. Epigenetics and finger regulators can be used for multiplex engineering of many cell types, including CAR-T cells and CAR-T regs, and have the potential to be deployed for both ex vivo and in vivo applications. I'm honored and privileged to represent the dedicated and innovative team of scientists at Sangamo. I'm convinced that our robust pipeline of preclinical programs and platform capabilities will serve Sangamo well in the years to come and deliver on our mission to translate groundbreaking science into medicines that transform patients' lives. I will now turn the call over to our Chief Financial Officer, Prathusha Durabadu, for an overview of our financial results. Prathusha?
spk02: Thank you, Jason, and good afternoon. Our detailed financial results for this quarter are available in the press release issued this afternoon, which can be found on our website. We ended the quarter with approximately $364 million in cash, cash equivalents, and marketable securities, which we believe will enable continued execution across our platform and programs. As we navigate through these turbulent market conditions, we continue to excise financial diligence and focus our investment in three key areas. advancement of our clinical programs, including February and PX200, progression of our preclinical CAR-T rig and CNS pipeline, and optimization of our in-house manufacturing capabilities. Additionally, since the start of the second quarter through today, we have raised approximately $40 million in net proceeds under our previously announced at-the-market offering program. This reflects our proactive approach to balance capital raises in these uncertain markets and speaks to the continued investor interest in our company. Turning to our 2022 full-year guidance, we continue to expect our 2022 full-year non-GAAP operating expenses to be between $280 million to $310 million. This rate excludes estimated non-cash stock-based compensation expense of approximately $40 million. We expect a significant portion of our operating expenses to be invested in continued advancement of our LEED programs, including February Phase 3 planning activities, Phase 1-2 activities for TX200, and preclinical work in CAR T rates and neurology genome engineering indications. We also expect to continue our investment in sickle cell disease following transition of the program back to Sangamo. I'll now turn it over to our CEO, Sandy, for closing remarks.
spk11: Thank you, Pratisha. 2022 continues to be a year of significant momentum for Sangamo. We are a clinical stage genomic medicine company with powerful innovative science. strong clinical execution capabilities, and deep experience developing INDs supported by in-house manufacturing to meet the needs of our growing pipeline. We continue to bring these capabilities together to create hope among the patients we're working to serve, a bright future for their company, and the potential for long-term sustainable value for our shareholders. I am very grateful to our leadership team and all my Sangamo colleagues for their dedication and hard work toward our mission of creating transformational new medicines for patients. We look forward to sharing anticipated key milestones and catalysts throughout the second half of 2022, including additional Phase 1-2 data from our Fabry study, dosing of additional patients in our Phase 1-2 study for sickle cell disease, and Phase 1-2 TX200 CAR T-REG study, and Pfizer's resumption of dosing in the Phase III trial in Haemophilia A. So at this time, we'd like to open it up for questions. Operator.
spk07: Ladies and gentlemen, if you have a question or a comment at this time, please press the star 1-1. We'll pause for a moment while we compile our Q&A roster.
spk06: Our first question comes from Greg Harrison with Bank of America. Your line is open.
spk09: Good afternoon. Thanks for taking our questions. First off, what should we be expecting from the next update from the TX200 program? Do you have a sense of how much follow-up duration and what other data points would you really need to see to establish proof of concept there?
spk11: Thank you for your question. We're very pleased to be driving forward with TX200 and delighted that the first patient has done so well and is four months out as safe. Rob, what's the plan going ahead?
spk14: As we've indicated in the call, we plan to complete the first dose cohort in 2022, and we will provide further updates once we have a meaningful package of data disclosed from that first complete dose cohort.
spk11: We understand the excitement around this program and that there are a number of Treg companies and that we all see CAR Tregs as potentially important medicine. So we look forward to sharing the results at the appropriate time.
spk09: Got it. Thanks. And then one more question, if I can. How does your base editor compare with the CRISPR-based approach, and where could you be differentiated?
spk11: Jason, this sounds one for you.
spk10: Yes. Thank you for the question. We're very excited about the capabilities of our base editor. We think that it adds another dimension to the toolkit that we have. That includes nucleases, now base editors, transcriptional regulators that can either increase or decrease the expression of genes in a tunable way. So, you know, our view is that having all of these tools is critically important to creating relevant therapeutics. One of the differentiating features of our base editor is its compact size. And that allows us to deploy it using a variety of delivery vehicles, including AAB delivery. So, you know, given that range of tools, we think that we are able to address almost any need when it comes to genetic engineering, and we're really excited about it.
spk09: Great.
spk06: Thanks again for taking the questions. One moment for our next question.
spk07: Our next question comes from with Wells Fargo. Your line is open.
spk19: Hi. Thanks for taking my questions. So maybe on the Fabry study, I'm curious about the reason behind escalating the dose to cohort four dose. We've seen data from the first two dose cohorts, and I thought the data was quite impressive. even with those low doses. And then you did the cohort three, obviously. And for the optional cohort four, you elected to further dose escalate. I'm wondering what are you trying to optimize with this higher dose, and what's the desired outcome there? Thanks.
spk11: Thanks for the question. We agree with you that the first two doses look very good. We've always planned to go up to 5E13. We decided to do it prudently in four steps and we're looking forward to showing the data from the full trial as soon as possible. There are a series of medical meetings later this year that we will show more of the data. The safety profile was very, very benign, unremarkable, and that allowed us to fulfill the full expansion of the dose exploration.
spk19: Got it. That's super helpful. And on the TX200, just a quick question about the safety profile. I think you mentioned that the first patient has been treated and followed, and so far there hasn't been any AEs concerning That's great to hear. Of course, we're familiar with CAR-T and CRS and all those kind of AEs associated with CAR-T. CAR-T reg is a very different kind of therapy. So what might be the AEs of interest that you are actively monitoring? Thanks.
spk11: Thank you. Rob?
spk14: We haven't seen any treatment-associated AEs so far, but One might expect potentially cytokine release types of reactions. It's an autologous product, so that's not very likely, but those are the things we're monitoring for. If the body's reacting to the introduction of an engineered CAR-T reg, even though it's the patient's own CAR-T, but I want to emphasize that we have not had any treatment-associated adverse events, but
spk11: It's the reason we do these studies in a very methodological way and take time between each patient, isn't it?
spk14: It is. We're very cautious because this is a groundbreaking revolutionary therapy to deliver a CAR-T reg, and we'll understand the full impact of that as we progress with the trial.
spk19: Got it. Thank you for taking my questions.
spk07: One moment for our next question. Our next question comes from Nicole Germino with Truist. Your line is open.
spk04: Hi, this is Dhoni Shah. I'm on for Nicole. Regarding Fabry disease, you have additional sites in Canada, Italy, and Australia. Can you talk about the market opportunity for Fabry in those geographies, if successful? And if you are successful, how do you plan on commercializing the gene therapy? And then I have follow-up.
spk11: Okay, so there's two questions, one about the clinical study and one about the commercialization. So Bettina, if you take the clinical study and Mark, then you take the second one.
spk13: Absolutely. So thank you for the question. Yes, we have opened sites now in additional countries. And as you point out, that is Italy and Australia and Canada. We have now 16 sites open in our Fabry study, which positions us well for enrollment in our expansion phase that we are now entering. I will hand it over to Mark.
spk11: And Bettina, we've seen a great deal of interest from patients.
spk13: Absolutely. In fact, the early data we have shown and the interactions with the investigators has shown us that there is a lot of interest from patients. We are now screening more and more patients as we go along. And this is beyond the classic male patients who were part of the initial dose escalation criteria. We are now open to enrolling female patients, patients with cardiac and renal involvement. And as such, there is interest also from these patient populations.
spk05: So I'm just picking up from Bettina. You know, obviously, as Bettina sort of summarized, our commitment is really to ensure that we, you know, successfully execute against the expansion cohort and plan for our phase three. You know, Fabry disease is not a disease that's just unique to the United States. It's a disease that comes out of a variety of different markets. So both the way we're approaching our clinical trial and the way we're approaching our plans for commercialization, take that into consideration. As you know, we've not guided any specifics in terms of our plans for commercialization, but we'll do that at the appropriate time.
spk04: Great. Thanks. And just a second on collaboration. Maybe can you talk about high level about your partner program progress? Kind of which part of the platform you're getting more attention from partners and where should we stay focused on? Thank you.
spk05: So one of the blessings about having, you know, unique technology platform is that we're constantly being approached with people exploring ways that they can collaborate with us. whether that be in terms of our gene engineering capabilities that Jason briefly touched on, whether that be opportunities to work together on capsid development or capsids that could be applied to our CNS programs. And so that's a key part of our focus from a business development standpoint. But in addition, as we've talked about in the past, we've raised about $815 million And in, you know, potentially six to seven billion in royalties that come from partners that, you know, approach us about utilizing our technology to take that technology into areas that we wouldn't otherwise do. And so I think the Biogen and Novartis continue to be, you know, great examples of that. And as we continue to confirm and validate our progress with our technology, we would expect other companies to, approach us with ideas that they might have in terms of how they could utilize our technology, and we'd be pleased to have those conversations.
spk06: Great. Thank you. One moment for our next question. Our next question comes from Gina Wang with Barclays. Your line is open.
spk17: Hi. Good evening, team. This is Hershita on for Gina. Thanks for taking our questions. We had one on TX200 and then a follow-up on Fabri, if I may. Could you remind us again what you hope to green from the biopsy data for TX200? If you remember correctly, I think, Jason, one of the things you mentioned previously was, you know, biopsy data will show whether The Tregs are trafficking and accumulating in the kidneys, so I was hoping you could elaborate on this point, and then I'll ask the Fabry question after.
spk11: Jason, as you're an immunologist, can you help us with what we may see in the kidney?
spk10: Yeah, I think you have that exactly right. That's what we'll be looking for. You know, there are a few things. One will be localization of the cells to the kidney. And the other will be evidence that the cells are having some effect on the local microenvironment in the kidney. So those are both things that we'll be looking for using both immunohistochemistry and in situ hybridization. And we'll be excited to share data as we assemble it into a meaningful data package.
spk11: And more simply or prosaically, we'll also be ensuring that there's no signs of kidney rejection or inflammatory damage to the kidneys. So safety is very important in studies like this.
spk17: Makes sense.
spk11: Thank you. And you had a question on Fabric?
spk17: Yes, yes, thanks, Sandy. So on Fabi, a quick clarification. The two additional patients that came off ERT, which cohorts were these patients in? Apologies, I missed that bit and prepared remarks. And also, if you could level set, you know, what kind of data can we expect at the conference later this month? You know, follow up and any other metrics or details you can highlight. That would be helpful. Thank you so much.
spk11: Thank you. Bettina, can you help us with this?
spk17: So we now have.
spk11: Bettina?
spk13: Absolutely. Sorry about that. So we now have a total, just as a reminder, a total of nine patients dosed, five of whom were dosed as they were on ERT. And of these five patients, four patients have now withdrawn from ERT. And that is one patient in cohort one, the only one who was on ERT upon entering the study, the one ERT subject in cohort two who was on ERT, and two out of the three patients in cohort three who were on ERT. And just as a reminder, cohort four patients, the two patients who were those in cohort four are naive patients. And so what we will be, to answer your second half of the question, what we'll be presenting later this month at SSIEM is incremental data. We will have data on six patients who are dosed based on the cutoff. And as a reminder, we had four patients presented in that world. And so we'll have incremental data also from those four patients.
spk11: And there are other potential times to show data later in the year?
spk13: Absolutely. We're planning additional data cuts and additional incremental data to be shared later at conferences later in this year.
spk17: Great. Thank you so much.
spk07: One moment for our next question.
spk06: Our next question comes from Ben Burnett with Stiefel. Your line is open.
spk03: Hi. This is Carolina Ibanezon. I'm Ben Burnett. Thank you for taking our questions. One follow-up on the previous question of Fabry to say Could you comment on the background of the patient's dose in cohort three and how, you know, their characteristics compared with patients in previous cohorts in terms of classical Fabry disease and biomarker levels?
spk11: So you're looking for some kind of background of the patients in cohort three?
spk13: Correct, yes.
spk11: Bettina?
spk13: Sure. So I think I would... point out that we are presenting detailed data at the end of this month. What I can say is reiterating what I've mentioned. Some of these patients are on ERT, some are not. The disease has different potential mutations, so there are different mutations for each of these patients. But patients do have underlying classic symptoms of Fabry. I think this is probably not the location to go into a lot of detail here, but suffice it to say that the in-depth data will be presented at SSIEM at the end of this month.
spk11: Was there a particular attribute or characteristic that you were trying to understand?
spk03: Well, you already touched on those. whether it was representing, you know, classic Fabry characteristics, and also if you could comment on biomarker levels.
spk11: So, I think we'll hold the biomarker levels for SSIEM, and we hope you'll be able to attend or view those. And then, as we've now also dose cohort four, and then this month are about to dose another two patients, with six that we're queuing up, you can understand that there'll be a constant flow of data throughout the rest of the year.
spk03: Understood. Looking forward to your next data update. Thank you.
spk07: Thank you. One moment for our next question. Our next question comes from Ritu Barwal. Calvin, your line is open.
spk18: Good afternoon, guys. Thanks for taking the question. Can you remind me of the target enrollment for your 5V13 expansion cohort in Fabry? And what is your target profile for that patient group? Really sort of the same question as cohort three, but really applied to the expansion cohort. And then I have a follow-up on Fabry CMC.
spk11: Yes, Bettina.
spk13: Yes, thank you. So the expansion phase of the study is going to enroll up to around 30 patients. We are targeting on enrolling not only male patients, but also female patients. This will be the first opportunity to enroll female patients and patients who may have cardiac involvement or renal involvement predominantly. So this will allow us to really cover the essential aspects of Fabry disease.
spk18: So it's more of a sort of a clinical presentation rather than any particular mutation subtype that you want to diversify for?
spk11: That's correct. Correct.
spk18: Okay. Got it. And then any target number of females?
spk13: There is no particular target, although we are seeing interest from this patient population. So we anticipate enrolling several female patients and several female patients are already in screening, in fact.
spk11: This will be the first time that a female fabric patient has been treated. And it's been interesting to learn of their passion for treatment. They feel they've been not they've been overlooked, and that they too have an important disease. And so it will be exciting to see that data.
spk18: Got it. And can you comment on CMC readiness for phase three start? Obviously, you know, CBER has said, please go into phase threes with your commercial product. You know, how are you with assay development, validation, that sort of thing?
spk13: So phase three planning is in progress. I think that's That's as far as we'll be talking about that at this point, but suffice it to say we've had and we're preparing for additional interactions with agencies and therefore we're well underway with phase three planning.
spk18: Got it. And a more expansive question, last one I promise, Sandy. One of the more, I guess, spicy sessions at ASGCT was on reimbursement. And one of the things that the European, one of the European advisors said was that they are working together to develop phase three designs that were meaningful to European payers, given the challenges of gene therapies in Europe, getting them paid for in Europe, as we've seen. Any thoughts on that, Sandy, as you think about phase three harmonization and development, you know, nothing in particular, nothing binding, but what should we be thinking about as that develops?
spk11: I'm going to pass the spicy question to Mark. But just before he answers, to complete the last question, the CMC readiness, the ASCII readiness, all under control, all set for phase three. So we're very, the team have been working hard in the background to get all these things ready. Mark.
spk00: Great.
spk11: We've been working hard in the background to get all these things ready. Mark.
spk05: Great. Yeah, so thanks for the question. I mean, you know, I think we all understand the requirements of the European payer environment. And, you know, I think, you know, one of the things that I feel we need to do is not only focus on the clinical endpoints around the disease itself, but the impact that this has, you know, treating the disease has on the burden of illness on society. And so again, you know, there are other competitors that are further ahead around commercialization in Europe. One in particular that's guided that, you know, they really want to take a look at the overall benefit to reduction in burden and cost to the healthcare systems in Europe to justify their pricing for their gene therapy. I think that's one model that one could approach to prove that actually treating these patients defers costs that are being expended by the same payers, obviously, in Europe, but just in other parts of the healthcare system versus whether it's hospitalizations or other treatments. So I think that data is going to be very important to collect with any gene therapy program, and certainly we're taking that into consideration as we evaluate the types of data that we want to collect in our studies.
spk18: Great. Very helpful. Thank you, guys.
spk06: And one moment for our next question. Our next question comes from Luca Issy with RBC. Your line is open.
spk16: Oh, excellent. Thank you for taking our questions. This is Lisa on for Luca. First off, congrats on all the progress on the quarter. Just a couple on Sabry. Wondering if you can remind us again what the criteria is for stopping ERT. And I believe you mentioned in the prepared remarks that you were in discussions with a fifth patient who was looking to stop ERT. I was just wondering if they are also in the cohort three group.
spk11: Thank you. So Bettina, criteria for stopping ERT and who's the fifth patient?
spk13: So the criteria for stopping ERT really have not been outlined in detail in the protocol intentionally to leave this, in this phase one, two study open to the investigator in conjunction with the patient. And so it is criteria. that those entities apply when they discuss this in conjunction with ourselves as well. The fifth patient is currently in discussion for ERT withdrawal.
spk11: So who is that fifth patient? It's in cohort three. So it's the third patient in cohort three and the two patients in cohort four are not on ERT. Correct.
spk16: Okay, got it. Thank you so much. And maybe, I'm not sure if you had said this before in the past, but just as you move to the dose expansion phase, are you going to be including kidney biopsies in the expansion phase?
spk13: Yes, indeed. We're going to be including kidney biopsies in patients who are naive or pseudonaive. We're performing that. In fact, we have already performed kidney biopsies on the two naive patients in cohort four, and so hope in the first half of next year to be sharing data from those first two patients.
spk16: Excellent. Thank you for taking our questions.
spk07: And one moment for our next question. Our next question comes from Maria Raycroft with Jefferies. Your line is open.
spk21: Hi, thanks for taking my questions. I have one for Fabry, too. Just wanted to check at what other conferences could we expect to see the full nine patients for Fabry? And just clarifying if we'll see the data for the full nine patients in the second half of this year.
spk11: Thanks for the question. There are several conferences coming up this year and into the beginning of next year. We're always cautious to not detail which conference we are going to until we have confirmation that there'll be a presentation there. So for now, we're only guiding to SSIEM.
spk21: Okay. And will we see an update on online patients before the end of the year? We would hope so. Okay. Okay. And then... It looks like Pfizer's reiterating restarting dosing in third quarter of this year, but the pivotal data has been pushed back from second half to late 23 or early 24. Can you talk about why this data readout has been pushed back?
spk11: I think we would guide you to speak to Pfizer about that. They hold the, they communicate in all of this, but they continue to guide that they're due to start the study in March. this quarter.
spk07: Okay. Okay. Thanks for taking my questions. One moment for our next question.
spk06: Our next question comes from Jason Scheiss with HCW.
spk07: Your line is open.
spk08: Hi. This is Jason. I'm Patrick. So I guess the only question we have is around the hemophilia program. uh sorry the single cell program for bivv003 um so now that is wholly owned and kind of returned from sanofi back to sangamo are there any potential plans to then partner it out again and if so will you be waiting until the phase three trials design and when the plans are ready um or will that be before that um planning thank you march you want to take this one sure
spk05: Yeah, so as Rob covered in his part of the talk, I mean, our focus now is to, you know, complete the precision phase one study, and then we'll evaluate that. At the same time, we're putting together plans for manufacturing as well as preparation of the phase three study design. You know, once we've seen the data and take a look at that relative to the, you know, the competitive data sets, which you know very much about, we will make a decision on how we commercialize or whether we look for a partner. You know, just to reemphasize that, you know, this is a debilitating disease. You know, there's roughly just, you know, just in the U.S. alone, 20,000 to 30,000 patients that have severe disease. And so, one of the things you need to remember is as we, as we see approvals in this space, and hopefully we will, it's going to take some time for us to service that population because you're constrained by your ability to manufacture their personalized cell therapy. And so we'll provide an update on that. You know, in terms of our rationale behind partnering, we really look at partners where we believe that we can get the medicine to patients in a quicker timeframe globally. And so, you know, as we do with all of our programs, if there's a partner that can allow us to do that faster and at the same time ensure that we're getting the right level of return for ourselves and our investors, that we'll do that.
spk06: All right. Thank you. One moment for our next question. Next question comes from . Your line is open.
spk20: Great. Good afternoon. Thanks for taking our questions. We're going to switch it up from Fabry and turn to Sickle Cell. Can you remind us what data you've seen that differentiates this program from the other gene therapy competitors? And can you repeat the comments around VOCs and your prepared remarks? What can we expect from the phase one data list this year, and when do you plan to collect data outside of VOC that focuses more on prevention of progressive organ damage? Thanks.
spk11: So, thank you for your question. We've dosed five patients now and are looking forward to seeing the data from them and the subsequent patients. And only once we've seen that will we be able to make any rational comment on differentiation. I also think it will take a larger population of patients to properly understand that.
spk06: Does that answer your question?
spk20: Yeah, that was one of them. And in the prepared remarks, I didn't catch it, but there were some comments around VOCs. If you could clarify that. And then as far as what data we can expect, you know, a lot of the community is focusing on VOCs, but less is focused on prevention of progressive organ damage, which is a pretty important aspect. Do you plan to collect data? And if so, when, at what point would you plan to collect data on that? Thanks.
spk11: So, Bettina, can you clarify about the VOC? And then I'll make additional comments.
spk13: Sure. So for the VOCs, we had already mentioned one patient out of the four patients dosed that we presented at ASH last year had one VOC. This patient has had a second VOC, and that's a patient who had the lowest hemoglobin levels. It's important to mention that that patient is now doing well and that all the other patients have not presented any VOCs. and are doing remarkably well.
spk11: And that patient was dosed with the original process, which the fifth patient and subsequent patients will be dosed with a much improved form that increases the long-term progenitors. I think you make a good point that VOCs, though, are very important. As a doctor, having treated patients with VOCs, it's a horrible disease, and the patients suffer greatly from it. But there's also a second underlying, whether it's a micro VOC type damage that you get that results in these patients having significantly shortened life expectancies. And we would hope that over the course of the trials and longer study, we would also show a benefit for that. But that's going to be a harder, longer time thing to prove but it clearly is important to the patients and it speaks to treating them as as young as possible so as they do not accumulate damage before they get this remarkable treatment great thanks for the clarity on that thank you and i'm not showing any further questions this time i turn the call back to louise for any closing remarks thank you once again for joining us today and for your questions
spk01: As a reminder, you can access the earnings release and presentation on the investor relations section of the FANGMA website. We look forward to keeping you updated on our future development.
spk07: Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.
spk12: The conference will begin shortly. To raise your hand during Q&A, you can dial star 11.
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