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'll be a question and answer session. To ask a question during the session, you need to press Star one. I would now like to turn the call over to your host, Louise Wilkie. You may begin.
Good afternoon. I'm Louise Wilkie, Sangamo's Vice President of 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 Macrae, Chief Executive Officer, Mark McClung, Chief Operating Officer, Prathyusha Duraibabu, 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 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 pre-clinical programs to the clinic, 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 discuss today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically in our annual report on Form 10-K for the fiscal year ended December 31, 2021, as supplemented by our quarterly report on Form 10-Q for the fiscal quarter ended June 30, 2022.
The forward-looking statements dated 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 Macrae.
Thank you, Louise, and good afternoon to everyone on the call. Sangamo 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 pre-clinical progress. This quarter, we received endorsement from the Fabry phase I/II study's 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 nuclease modified autologous cell therapy for the treatment of sickle cell disease, formally completed the transition back to being a wholly owned Sangamo 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 I, II study in the third quarter of this year and 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 hemophilia A gene therapy study, Pfizer advised us that it expects to resume dosing in the AFFINE trial in the third quarter of 2022, with a pivotal readout estimated in late 2023 or early 2024. I was thrilled to attend and see the reaction to Sangamo's important contributions at the American Society of Gene & 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 recognize the difficult market conditions, though, being experienced across the industry. We believe Sangamo's 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. With that, I'd like to turn the call over to our Head of Development, Rob Schott, who will discuss the data from our clinical programs in more detail. Rob?
Thank you, Sandy. 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 I/II STAAR study evaluating isaralgagene civaparvovec, or ST-920, our wholly owned gene therapy program for the treatment of Fabry disease in adults. Two additional patients were withdrawn from enzyme replacement therapy, or ERT. Out of the five patients that began the STAAR study on ERT, a total of four have now been successfully taken off ERT, one each in cohorts 1 and 2 and 2 in cohort 3, 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 the investigators have not required resumption of ERT.
As Sandy mentioned, this quarter, the safety monitoring committee for the STAAR study endorsed progressing from the phase I/II 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 I/II STAAR 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 III 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 I/II PRECIZN-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 I/II 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 I/II data update before the end of the year. In addition, phase III enabling activities, including manufacturing readiness, actively continue. Progress continued in the phase I/II 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, and 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 five in 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 T reg therapies that are working to develop to address a range of autoimmune conditions. In addition to TX200, Sangamo has an active pre-clinical 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 III AFFINE trial evaluating giroctocogene fitelparvovec, 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 that a 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?
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 capsid 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 ASGCT marked the unveiling of our compact and highly efficient zinc finger-based editor and the deployment of our epigenetic zinc finger regulators to engineer T-cells and other immune cell types. The zinc finger-based 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, allowing packaging into a single AAV vector.
This is a critical requirement for the efficient use in many therapeutic applications, particularly in vivo. The epigenetic zinc finger regulators can be used for multiplex engineering of many cell types, including CAR T cells and CAR-Tregs, 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, Prathyusha Duraibabu, for an overview of our financial results. Prathyusha?
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 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 exercise financial diligence and focused our investment in three key areas. Advancement of our clinical programs, including Fabry and TX200, progression of our preclinical CAR-Treg 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-$310 million. This range 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 lead programs, including Fabry phase III planning activities, phase I/II activities for TX200, and preclinical work in CAR-Treg and neurology genome engineering indications. We also expect to continue our investments 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.
Thank you, Prathyusha. 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 our 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 I/II study for sickle cell disease, phase I/II TX200 CAR-Treg study, and Pfizer's resumption of dosing in the phase III trial in hemophilia A. At this time, we'd like to open it up for questions. Operator.
Ladies and gentlemen, if you have a question or a comment at this time, please press Star one one. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Greg Harrison with Bank of America. Your line is open.
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?
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, is safe. Rob, what's the plan going ahead?
As we've indicated in the call, we plan to complete the first dose cohort in 2022. We will provide further updates once we have a meaningful package of data to disclose from that first complete dose cohort.
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. We look forward to sharing the results at the appropriate time.
Got it. Thanks. One more question, if I can? How does your base editor compare with the CRISPR-based approach, and where could you be differentiated?
Jason, this one's for you.
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, you know, 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. 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 AAV delivery.
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.
Great. Thanks again for taking the question.
One moment for our next question. Our next question comes from Yanan Zhu with Wells Fargo. Your line is open.
Hi. Thanks for taking my questions. 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. Then you did the cohort three, obviously. For the optional cohort four, you elected to further dose escalate. I'm wondering what you are trying to optimize with this higher dose, and what's the desired outcome there? Thanks.
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 benign, unremarkable, and that allowed us to fulfill the full expansion of the dose exploration.
Got it. That's super helpful. 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. You know, of course, we're familiar with CAR T and CRS and all those kind of AEs associated with CAR T. CAR-Treg is a very different kind of therapy. What might be the AEs of interest that you are, you know, actively monitoring? Thanks.
Thank you. Rob.
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. Those are the things that we're monitoring for. If the body's reacting to the re-introduction of an engineered
CAR-Treg, even though it's the patient's own CAR-T. I wanna emphasize that we have not had any treatment-associated adverse events.
It's the reason we do these studies in a very methodological way and take time between each patient, isn't it?
It is. We're very cautious 'cause this is a groundbreaking, revolutionary therapy to deliver a CAR-Treg, and we'll understand the full impact of that as we progress with the trial.
Got it. Thank you for taking the questions.
One moment for our next question. Our next question comes from Nicole Germino with Truist. Your line is open.
Hi, this is Nishant. 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 then? You know, if you are successful, how you plan on commercializing the gene therapy? I have follow-up.
Okay. It sounds like there's two questions, one about the clinical study and one about the commercialization. Why don't, Bettina, if you take the clinical study, and Mark, then you do the second one.
Absolutely. Thank you for the question. Yes, we have opened sites now in additional countries. 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're now entering. I will hand it over to Mark to-
Bettina, we've seen a great deal of interest from patients.
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're now open to enrolling female patients with cardiac and renal involvement. As such, there is interest also from these patient populations.
Just picking up from Bettina, you know, obviously, as Bettina's sort of summarized, our commitment is really to ensure that we, you know, successfully execute against the expansion cohort and plan for our phase III. You know, Fabry disease is not a disease that's just unique to the United States. It's a disease that comes from a variety of different markets. 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, you know, guided any specifics in terms of our plans for commercialization, but we'll do that at the appropriate time.
Great. Thanks. Just a second and 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, you know, where should we stay focused on? Thank you.
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, you know, to work together on capsid development or capsids that could be applied to our CNS programs. You know, that's a key part of our focus from a business development standpoint.
In addition, as we've talked about in the past, you know, we've raised about $815 million, and in, you know, potentially $6 billion to $7 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. I think Biogen and Novartis continue to be, you know, great examples of that. 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.
Great. Thank you.
One moment for our next question. Our next question comes from Gena Wang with Barclays. Your line is open.
Hi, good evening, team. This is Rashida on for Gena. Thanks for taking our questions. We had one on TX200, and then a follow-up on Fabry, if I may. Could you remind us again what you hope to gain from the biopsy data for TX200? If I 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.
Jason, as you're our immunologist, can you help us with the what we may see in the kidney?
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. Those are both things that we'll be looking for using both immunohistochemistry and in situ hybridization. We'll you know be excited to share data as we assemble it into a meaningful data package.
And, and-
Great.
More simply or prosaically, we'll also be ensuring that there's no signs of kidney rejection or inflammatory damage to the kidneys. Safety is very important in studies like this.
Makes sense. Thank you.
And you had a-
Yeah. Sorry, I had a quick.
You had a question on Fabry.
Yes, yes. Thanks, Sandy. On Fabry, a quick clarification. The two additional patients that came off ERT, which cohorts were these patients in? Apologies, I missed that bit in prepared remarks. 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.
Thank you. Bettina, can you help us with this?
We now have.
Bettina?
Absolutely. Sorry about that. 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. Of these five patients, four patients have now withdrawn from ERT. That is one patient in cohort 1, the only one who was on ERT upon entering the study. The one ERT subject in cohort 2 who was on ERT, and two out of the three patients in cohort 3 who were on ERT. Just as a reminder, cohort four patients, the two patients who were dosed in cohort 4 are naive patients. 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 cut-offs. As a reminder, we had four patients presented at WORLD Symposium. We'll have incremental data also from those four patients.
There are other, potential times to show data later in the year.
Absolutely. We're planning additional data cuts and additional incremental data to be shared later at conferences later in this year.
Great. Thank you so much.
One moment before our next question. Our next question comes from Benjamin Burnett with Stifel. Your line is open.
Hi, this is Carolina Ibañez on Benjamin Burnett. Thank you for taking our questions. One follow-up on the previous question on Fabry disease. Could you comment on the background of the patients dosed in cohort 3 and how their characteristics compare with patients in previous cohorts in terms of classical Fabry disease and biomarker levels?
You're looking for some kind of background of the patients in cohort three?
Correct. Yeah.
Bettina.
Sure. 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. 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. Suffice it to say that the in-depth data will be presented at SSIEM at the end of this month.
Was there a particular attribute or characteristic that you were trying to understand?
Well, you already touched on whether it was representing, you know, classic Fabry characteristics and also if you could comment on biomarker levels?
I think we'll hold the biomarker levels for SSIEM, and we hope you'll be able to attend or view those. Then as we've now also dosed for cohort 4, 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.
Understood. Looking forward to your next data update. Thank you.
Thank you.
One moment for our next question. Our next question comes from Ritu Baral with Cowen. Your line is open.
Good afternoon, guys. Thanks for taking the question. Can you remind me of the target enrollment for your 5e13 expansion cohort in Fabry? 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. I have a follow-up on Fabry CMC.
Yes, Bettina.
Yes, thank you. 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. Patients who may have cardiac involvement or renal involvement predominantly. This will allow us to really cover the essential aspects of Fabry disease.
It's more of a, sort of a clinical presentation rather than any particular mutation subtype that you want to diversify for?
That's correct.
Correct.
Okay. Got it. Any target number of females?
There is no particular target, although we are seeing interest from this patient population. We anticipate enrolling several female patients and several patients. Female patients are already in screening, in fact.
This will be the first time that a female Fabry patient has been treated. It's been interesting to learn of their passion for treatment. They feel they've been overlooked and that they too have an important disease. It'll be exciting to see that data.
Got it. Can you comment on, CMC readiness for phase III start? Obviously, you know, CBER has said, "Please go into phase III with your commercial product." You know, how are you with, assay development, validation, that sort of thing?
Phase III planning is in progress. I think that's as far as we'll be talking about that at this point. Suffice it to say we've had and we're preparing for additional interactions with agencies and therefore we're well underway with phase III planning.
The CMC.
Got it. A more expansive question. Last one, I promise, Sandy. One of the more, I guess, spicy sessions at ASGCT was on reimbursement. One of the things that one of the European advisors said was that they are working together to develop phase III designs that were meaningful to European payers, given the challenges of gene therapies getting them paid for in Europe, as we've seen. Any thoughts on that, Sandy, as you think about phase III harmonization and development? You know, nothing in particular, nothing binding, but what should we be thinking about as that develops?
I'm going to pass the spicy question to Mark. But just before he answers, to complete the last question, the CMC readiness, the assay readiness, all under control, is all set for phase three. We're very-- The team have been working hard in the background to get all these things ready. Mark.
Great.
We've been working hard in the background to get all these things ready. Mark.
Great.
Thanks for the question. I mean, you know, I think we all understand the requirements of the European payer environment. 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. 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 wanna 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 you know, treating these patients, defers costs that are, you know, are being expended by the same payers, obviously, in Europe, but just in other parts of the healthcare system versus, you know, whether that's hospitalizations or other treatments. I think that data is gonna 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 wanna collect in our studies.
Great. Very helpful. Thank you, guys.
Okay, one moment for our next question. Our next question comes from Luca Issi with RBC. Your line is open.
Excellent. Thank you for taking our questions. This is Lisa on for Luca. First off, congrats on all the progress in the quarter. Just a couple on Fabry. Wondering if you can remind us again what the criteria is for stopping ERT. I believe you mentioned in the prepared remarks that you were in discussions with a fifth patient who is looking to stop ERT. I was just wondering if they are also in the cohort three group. Thank you.
Bettina. Bettina, criteria for stopping ERT and who's the fifth patient?
The criteria for stopping ERT really have not been outlined in detail in the protocol intentionally to leave this in this phase 1/2 study open to the investigator in conjunction with the patient. 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.
Who is that fifth patient? Is it?
That fifth patient is in cohort 3.
Cohort 3.
Yes.
It's the 3rd patient in cohort 3, and the two patients in cohort 4 are not on ERT.
Correct.
Okay. Got it. Thank you so much. 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?
Yes, indeed. We're going to be including kidney biopsies in patients who are naive or pseudo-naive. We're performing that. In fact, we have already performed kidney biopsies on the two naive patients in cohort 4 and so hope in the first half of next year to be sharing data from those first two patients.
Excellent. Thank you for taking our question.
One moment for our next question. Our next question comes from Maury Raycroft with Jefferies. Your line is open.
Hi. Thanks for taking my questions. I had 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.
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. For now we're only guiding to SSIEM.
Okay. Will we see an update on all nine patients before the end of the year?
We would hope so.
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 2023 or early 2024. Can you talk about why this data readout has been pushed back?
I think we would guide you to speak to Pfizer about that. They communicate in all of this, but they continue to guide that they're due to start the study in this quarter.
Okay. Thanks for taking my questions.
One moment for our next question. Our next question comes from Jason [inaudible] with H.C.W your line is open.
Hi, this is Jason on for Patrick. The only question we have is around the sickle cell program for BIVV003. Now that it's 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 trial design and when the plans are ready? Or will that be before that planning? Thank you.
Mark, do you want to take this one?
Sure. Yeah. As Rob covered in his part of the talk, I mean, our focus now is to, you know, complete the PRECIZN-1 phase I 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 III 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. One of the things you need to remember is as we see approvals in this space, and hopefully we will, it's gonna take some time for us to service that population because you're constrained by your ability to manufacture their personalized cell therapy. 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.
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, then we'll do that.
All right. Thank you.
One moment for our next question. The next question comes from Andreas Argyrides with Wedbush. Your line is open.
Great. Good afternoon. Thanks for taking our questions. We're gonna 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? Can you repeat the comments around VOCs in your prepared remarks? Also-
What can we expect from the phase I data readout this year? When do you plan to collect data outside of VOC that focuses more on prevention of progressive organ damage? Thanks.
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. 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. Does that answer your question?
Yeah, that was one of them. In the prepared remarks, I didn't catch it, but there were some comments around VOCs, if you could clarify that. 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? If so, at what point would you plan to collect data on that? Thanks.
Bettina, can you clarify about the VOC? I'll make additional comment.
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.
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. There's also a second underlying, whether it's a micro VOC type damage that you get in that results in these patients having significantly shortened life expectancies. We would hope that over the course of the trials and longer study, we would also show a benefit for that. That's gonna be a harder, longer time thing to prove.
It clearly is important to the patients, and it speaks to treating them 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.
I'm not showing any further questions at this time. I'd like to turn the call back to Louise for any closing remarks.
Thank you once again for joining us today and for your questions. As a reminder, you can access the earnings release and presentation on the investor relations section of the Sangamo website. We look forward to keeping you updated on our future developments.
Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.