Good day, thank you for standing by. Welcome to the Sangamo Therapeutics Third Quarter Earnings 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 will need to press star one one on your telephone. You will then hear an automated message advising that your hand is raised. Please be advised that this call is being recorded. I will now turn it over to Louise Wilkie, Head of Corporate Communications and Investor Relations. Please go ahead.
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 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, Nathalie Dubois-Stringfellow, Chief Development Officer, 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 on 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 patients, and presenting clinical data, advancements of our product candidates, advances of preclinical programs to the clinics, our investment focus, and the sufficiency of our resources, our 2022 financial guidance, upcoming 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 September 30, 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, Sandy Macrae.
Thank you, Louise, and good afternoon to everyone on the call. Sangamo will continue to pursue scientific innovation and development excellence in the third quarter as we progressed our mission of turning groundbreaking science into potentially transformative genomic medicines for patients. I am pleased with the momentum we are achieving across our programs, with our clinical data continuing to demonstrate the strength of our pipeline. Regarding our wholly-owned Fabry disease program, we were excited to present additional preliminary data from our Phase II/II STAAR study at three separate medical conferences since the last call. We continue to be encouraged by the promising data generated to date, showing sustained and elevated alpha-Gal A activity along with a favorable safety profile as of the last data cut in July.
These data demonstrate the potential of this therapy to replace the current standard of care and provide the potential for a one-time dosing alternative rather than a lifetime of ERT infusions. I'm also pleased to share that the study has moved into the dose expansion phase, and we've begun dosing patients, including the first female patients in the study. We continue to make progress in our wholly-owned sickle cell program this quarter, dosing the sixth patient in the Phase I/II PRECISION study. This is the second patient to be dosed with our product candidate manufactured using improved methods. In addition, the FDA has granted Regenerative Medicine Advanced Therapy, or RMAT, designation to our sickle cell product candidate. Momentum continues behind our Phase I/II STEADFAST study of TX200 in HLA-A2 mismatched kidney transplantation.
I'm pleased to announce that the second patient was successfully dosed in late September, while the first patient has reached 8-month post-infusion. Lastly, we jointly announced with Pfizer on September 22 that the Phase III AFFINE trial in hemophilia A had reopened recruitment. Trial sites resumed enrollment in September, and dosing expected to resume shortly. The resumption of this study is an important milestone as it takes us, with our partner Pfizer, one step closer to getting this potential treatment to patients in an area of significant unmet medical need. I'm proud of the team for the advancements we continue to make, staying true to our strategic focus on our research and development capabilities. Each incremental update brings us closer to our goal of creating transformative medicines for patients while creating long-term value for shareholders.
I'd like to turn the call over to our Head of Development, Nathalie, who will discuss the data from our clinical programs in more detail. Nathalie?
Thank you, Sandy, and good afternoon to everyone on the call. We had several promising updates in the third quarter and are pleased with the progress being made across our clinical programs. In Fabry, a fifth patient was withdrawn from enzyme replacement therapy in the Phase I/II STAAR clinical study, evaluating isaralgagene civaparvovec or ST-920, our wholly owned gene therapy product candidate for the treatment of Fabry disease.
This marked the 5th and final patient in the dose escalation phase who started the study on ERT to have been withdrawn from ERT. All subjects report they are not experiencing changes in symptoms and have not required resumption of ERT. After receiving endorsement from the Fabry Phase I/II study safety monitoring committee to progress to the dose expansion phase, 5 patients have been dosed in this expansion phase at the 5 to 13 mg per kg dose level, including the first two female patients in the study. Momentum also continue with additional patients currently in screening and awaiting dosing, including more female patients. Since the last call, we were proud to present updated preliminary Fabry data at three medical conferences.
In August, we presented data at the Society for the Study of Inborn Errors of Metabolism, SSIEM, annual meeting in Freiburg, Germany, presenting data on five patients as of February 14 data cut. Last month, we provided further updates at the 29th annual congress of the European Society of Gene & Cell Therapy, ESGCT, in Edinburgh, Scotland, as well as the National Organization for Rare Disorders, NORD, conference in Washington, D.C. At both these events, we presented data as of July 21, 2022, presenting for the first time data across all four dose cohorts in the dose escalation phase. All nine treated patients exhibited sustained elevated alpha-Gal A activity, ranging from nearly 2-fold to 30-fold of mean normal for almost two years of follow-up in the longest treated patient.
All patients exhibited above normal of alpha-Gal A activity by five weeks after dosing, and importantly, all four patients in long-term follow-up maintained elevated alpha-Gal A levels for one year or more. We remain encouraged to see durability of effect for this length of time. Also of note, four patients have undergone ERT withdrawal as of the cutoff date and continue to maintain elevated alpha-Gal A activity up to 28 weeks post-withdrawal. The two subjects with substantially higher elevation in plasma lyso-Gb3 pretreatment show a 40% and 55% reduction from baseline in lyso-Gb3 level, respectively, after ST-920 dosing. Importantly, ST-920 continued to be generally well tolerated in the nine treated patients with no treatment-related adverse event higher than grade one, except for one grade two pyrexia. No treatment-related serious adverse events were reported.
Of note, no subjects have been treated with steroids, either prophylactically or reactively, and there have been no liver enzyme elevation requiring treatment. Since our last call, additional sites in this global study have been opened, including the first in Asia-Pacific, and we're actively preparing additional new sites. You can expect further clinical updates from the STAAR study, including the first data from the expansion cohort in the first half of 2023. We continue to actively plan for a potential Phase III study and are engaging with health authorities, patient advocacy group, and investigators. In the Phase I/II PRECISION study of BIVV003, a zinc finger nuclease gene-edited cell therapy candidate for the treatment of sickle cell disease, now wholly owned by Sangamo, we dosed the sixth patient.
This is the second patient to have been dosed with a product candidate manufactured using improved methods shown in internal experiments to increase the number of long-term progenitor cells in the final product. We are pleased to continue to be making progress in the Phase I/II study and look forward for providing additional updates at an appropriate time. As Sandy mentioned earlier, on August 24th, the FDA granted Sangamo's request for Regenerative Medicine Advanced Therapy, or RMAT, designation for BIVV003. RMAT designation is granted to regenerative medicine therapy intended to treat, modify, reverse, or cure a serious condition for which preliminary clinical evidence indicates that this medicine has the potential to address an unmet medical need. The RMAT designation includes all the benefits of the Fast Track and Breakthrough Therapy designation program, including early interaction with FDA.
Furthermore, we were accepted to participate in a poster presentation at the upcoming 64th American Society of Hematology, or ASH, annual meeting and exposition taking place in New Orleans, Louisiana, December 10th-13th, 2022. We look forward to presenting updated clinical data then. Finally, Phase III study design, enabling activities, and manufacturing readiness are in progress. Progress continues in the Phase I/II STEADFAST study, our 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. The second patient was dosed in late September, and I'm pleased to report that the product candidate continued to be generally well tolerated in both patients. Two control patients have been enrolled and transplanted, demonstrating ongoing interest in the study.
We will provide further guidance on timing for dosing of the third patient. When the transplant has been scheduled and we have confirmed a potential dosing date. Finally, regarding the Phase III AFFINE trial evaluating giroctocogene fitelparvovec, an investigational gene therapy for hemophilia A, we jointly announced with our partner, Pfizer, that the trial has reopened recruitment. Trial sites resume enrollment in September, and dosing is expected to resume shortly. A pivotal readout is expected in the first half of 2024. In addition, with our partner Pfizer, we've been accepted to participate in a poster presentation at ASH, December 10-13, 2022, providing updated clinical data on the Phase I/II ALTA study. We look forward to sharing updated data in December. I will now turn the call over to our Chief Scientific Officer for updates on our preclinical research program. Jason?
Thank you, Nathalie, and good afternoon, everyone. I'm 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 our preclinical programs, as well as expanding our proprietary genomic engineering toolkit and developing novel AAV capsids to enable more effective therapeutically relevant delivery of these tools. The Sangamo team had multiple presentations at this year's European Society of Gene and Cell Therapy Annual Conference, including work describing the use of our proprietary zinc finger nuclease platform to engineer both allogeneic healthy donor regulatory T-cells and autologous B-cells. Additionally, data from preclinical studies performed with our collaborators at the Massachusetts Institute of Technology's Broad Institute were presented at the International Prion 2022 Conference in Göttingen, Germany this September.
We were thrilled to hear the strong feedback from key opinion leaders at the conference who expressed their excitement with the science and its potential for patients in need. This work demonstrated the ability of Sangamo's engineered zinc finger protein transcription factors to specifically reduce prion protein expression in the brain and significantly extend the survival in a mouse model of prion disease. We look forward to providing updates on this and other programs in the future. I will now turn the call over to our Chief Financial Officer, Prathyusha, for an overview of the financial results. Prathyusha?
Thank you, Jason, and good afternoon, everyone. 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 $350 million in cash equivalents, and marketable securities, which represents a net decline of $14 million from the prior quarter. This reflects our proactive approach to both prudent capital management and balanced capital raises in these uncertain markets and speaks to the continued investor interest in our company. We've raised approximately $75 million in net proceeds under our at-the-market offering program since the beginning of the year. We continue to focus our investments in three key areas, advancement of our clinical programs including Fabry, sickle cell, and TX200, progression of our preclinical CAR Treg and CNS pipeline, and optimization of our in-house manufacturing capabilities.
Turning to our 2022 full year guidance, we expect our full year non-GAAP operating expenses to be lower than previously guided and land between $280 million and $290 million. This range excludes estimated non-cash stock-based compensation expense of approximately $35 million. We expect a significant portion of our operating expenses to be invested in the continued advancement of our lead programs, including Fabry Phase III planning activities, Phase I/II activities for sickle cell disease and TX200, and pre-clinical work in CAR-Treg and genome engineering indications in the central nervous system. I will now turn the call back to Sandy for closing remarks.
Thank you, Prathyusha. We're pleased with our achievements during this quarter and the progress we have made across our clinical and pre-clinical pipeline. We are a clinical-stage genomic medicine company building momentum with our novel science, clinical execution, and in-house manufacturing. The progress this quarter takes us one step closer to delivering potentially transformative therapies for patients in need while creating long-term value for shareholders. I'm so proud of our team here at Sangamo who work tirelessly to advance our programs and carry out our mission.
We are delighted with the positive momentum and look forward to updating you in the near term with several expected milestones, including presentations to ASH of the updated Phase I/II data in sickle cell disease, presentation at ASH of updated Phase I/II data in hemophilia A, additional Phase I/II Fabry data in the first half of 2023, including additional ERT withdrawal data and the first data from the expansion phase, and dosing of the third patient in the STEADFAST Phase I/II study. At this time, we'd like to open up for questions. Operator, please open the line for questions.
Thank you. At this time, we will conduct the question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. Please stand by as we compile the Q&A roster. Our first question comes from Gena Wang with Barclays. Gena, your line is open.
Thank you for taking my questions. I have two questions. The first one is the sickle cell at the ASH, and then we all saw the abstract released early today. So it seems like a placeholder, a data cut-off May third. Just wondering at the full data presentation, will we see two more patients at ASH? And then my second question is the Fabry program. So regarding the expansion cohort data in first half 2023, will you share the five patient data, or will we see more patient data beyond currently enrolled those five patients? And also, what type of data will you be sharing? Would that be mainly on the biomarker data like alpha-Gal A and the lyso-Gb3? What kind of a clinical profile will be your goal to move to the next step?
Gena, good afternoon, and thank you for your question. As I understand, you're asking a question about sickle and a question about Fabry. I'm gonna pass sickle over to Nathalie, and then Bettina will cover the Fabry question. Nathalie.
Hi, good afternoon, Gena. Patient five in the trial was dosed in May 2022, and it was the first patient to receive a product candidate manufactured using the improved process. We expect to share early preliminary data from this patient at ASH in December via a poster presentation, along with an update of the first four patients' doses.
Gena, thank you for the question around Fabry. We are, as you have seen, very excited actually to be sharing that we have now dosed five patients in the expansion cohort. That brings us to a total of 14 patients dosed in the Fabry study, of which, if you do the math, it means we have seven patients treated at the highest dose level. We do believe ST-920 has the potential to provide an alternative to the current standard of care.
We will be sharing, as we pointed out, in the first half of 2023, data from both, additional data from the dose escalation as well as the early data from the expansion cohort patients, and this will include biomarker data as well as additional clinical data, the exact nature of which we will share in the first half, so in early 2023.
Thank you.
Please stand by for the next question. Our next question comes from Luca Moroni with RBC. Go ahead, Luca.
Oh, perfect. Thank you. This is Lisa on for Luca. Thank you so much for taking our question. Two on Fabry for you today. First is on the data. Just wanted to follow-up on the Fabry data presented at ESGCT last month. I think we noticed there was at least one patient who was withdrawn from ERT but subsequently had an increase in the plasma alpha-Gal A activity after the withdrawal. I was just wondering how we should rationalize this response, given you would expect that the alpha-Gal A levels to drop after the ERT withdrawal. Secondly is on the Phase III planning. You know, you said. You reiterated this today that a Phase III planning is underway.
Just wondering if you have had discussions with the FDA here on what a Phase III could look like, what would be the primary endpoint, and what you would need to show in terms of durability given this is a gene therapy approach. Thank you.
Thank you for your questions, and thank you for paying such attention to our ESGCT presentation. I'll help. I'm gonna pass this over to Bettina, but I'll help her a little with the second part. We've had a lot of time to plan and think about the Phase III study. We've spoken to the agency, and we'll share the details of that study nearer the time. Forgive me because I know how interested everyone is in the details of that study. Bettina, can you answer the first part?
Absolutely. Thank you so much for that question. On patients on ERT who have withdrawn from ERT, you asked about the alpha-Gal A activity expression. We do expect alpha-Gal A expression to be sustained over time, and that's what we are seeing, not only in patients who were naive or pseudo-naive, but also patients on ERT who were withdrawn from ERT. That is the objective of our therapy, and in fact, we believe that ST-920 has that potential to provide an alternative to the current standard of care of ERT. If you were referring to plasma lyso-Gb3 levels, these specific patients are all doing well. Their plasma lyso-Gb3 remains within the range seen in patients on ERT. The investigators are happy with the data, and the patients remain off ERT. I hope that addresses your question.
It does. Thank you.
I would encourage you to remember that this is cutting-edge clinical science. These are the first patients that we've gathered data on with this treatment, with the withdrawal of ERT, and the early data that you've seen is with the lowest dose response. We hope we plan to be withdrawing high dose, the dose we've chosen to go forward into Phase III and show patients withdrawn from ERT with that. The other thing I would ask you to think about is even for patients on ERT, when we added in our gene therapy, they showed additional benefit. I think this is sometimes overlooked.
Patients who'd been on ERT for a long time, who then got the gene therapy, reported feeling better, that they were sweating, and there was evidence of stabilization or even improvement of their cardiac function. Really speaking to the power of this medicine.
Please stand by for our next question. Our next question comes from Nicole Germino with Truist. Your line is open.
Hi, this is Alex from Nicole. For the CAR-Treg platform, would you consider out-licensing or engaging in other collaborations with Big Pharma? If so, could you provide some color on the types of partnerships that you would consider that might work best for Sangamo? Related, what are your thoughts on Big Pharma dropping some IL-2 programs that we've seen in the news in autoimmunity? Does this change or does this pave the way for CAR-Tregs in the space? Thanks.
Mark, you run our business development group. Would you want to talk to that?
Sure. Thanks for your question. You know, so obviously we're excited with the progress that we're making with T- regs, where, you know, we believe we're the first company to have dosed a patient, as we've communicated earlier. Our commitment is to continue to move forward with that study and drive it towards a, you know, proof of concept. You know, if companies do approach us, you know, similar to what we've done in the past, if they can bring resources, know-how, and funding actually to accelerate the therapy to patients faster than we can, we will always evaluate that. But we're not commenting on any current conversations that we might be having in that regard.
Thanks. Also we've seen in the news some big pharma dropping IL-2 platforms. Have you seen this and do you have any comments on that?
Jason, our Chief Scientific Officer. Jason, would you be able to comment on IL-2 and where we fit in among the range of T- reg programs?
Yeah. Thank you, Sandy, and thanks for the question. I think the latest news that I'm aware of on Big Pharma dropping an IL-2 program was related to the use of IL-2 in oncology, which is a different approach than some of the IL-2 muteins that are being explored to enhance T-reg biology. Whichever the case is, it's important to point out that while IL-2 muteins can be used to expand regulatory T cells and do offer a potential for therapeutic benefit in autoimmune disease, it's a fundamentally different approach because it relies on systemic delivery of that IL-2 and increasing regulatory T cells in the entire body of the patient.
The approach we're taking with CAR regulatory T cells is to target the regulatory biology and cells using the chimeric antigen receptor to the relevant tissue. That's a much different proposition where the kind of immune regulation that the regulatory T cells afford is directed in a kind of specific and very potent way towards the tissue where the autoimmune pathology is occurring. Moreover, the IL-2 muteins, despite best efforts, still do have some reactivity with effector T cells and NKT cells. This is confounding any interpretations of the effectiveness of those, because by also hitting effector T cells, one runs the risk of actually exacerbating autoimmune disease.
Thank you, Jason.
Thanks for all the color.
Please stand by for the next question. Our next question comes from Yanan Zhu with Wells Fargo. Your line is open.
Hi. Thanks for taking our questions. A question on Fabry and a question on sickle cell program. For the Fabry, ESGCT presentation, I think you alluded to this earlier. Looks like the lyso-Gb3 levels increased in patients who discontinued ERT. But since that data cutoff is rather early, July 21, 2022, it's been quite a few months since that data cutoff. I think you mentioned nobody has resumed ERT. I was just wondering, could we take that as meaning those patients have somehow stabilized their lyso-Gb3 levels? Could you also remind us what's the criteria for resuming ERT? Thanks.
Thank you. Thank you for your question as always. Bettina, can you give us some clarification on that, please?
For sure. Thank you for that question. We were very pleased to present the latest Fabry data at ESGCT. I can confirm that.
We now have five patients who are off ERT and that none of them have resumed ERT therapy. The investigators are happy with the data they are seeing, including the plasma lyso-Gb3 data they are seeing. In terms of criteria for resumption of ERT, that is really dependent on a series of biomarker and clinical data, and ultimately a decision of the investigator with the patient. So far, those patients are doing well.
I think that's the most important thing, that it's an investigator call. The patients are doing well, and therefore the investigator is confident to keep them off, and that the levels you've seen are similar to what other patients on ERT would have for their lyso-Gb3.
Indeed.
Got it. That's very good to hear. For the sickle cell program, you know, you talked about Phase III design and manufacturing readiness are underway. I was wondering how much of those progress has been informed by what you saw in patient number 5, the patient on the new manufacturing product. Also, do you plan to pursue this program by yourself or how urgent is it to find a partner for this program? Thank you.
Nathalie, can you answer that one?
Thank you for your question. We're currently focused on completing the Phase I/II study and Phase III enabling activities. We're really excited to have this program in hand, and we're planning to take this program forward, assuming the data continue to support a Phase III program. The second cohort of those next patients that have. It's not a cohort, sorry. The next patient that have improved manufacturing will be very informative to see if we if we have a body of evidence to continue to Phase III. We're planning ahead and you'll have to wait for ASH poster to see a little bit more data.
Got it. Partnership incentives, initiatives?
Our intention is always to do the best for the program. Our intention is to gather the data, and so we won't really see the full data set from the new improved process until first quarter, first half of next year. At that point, we'll make the necessary decision. We're looking at is whether we do it or whether a partner does it's getting a successful medicine to patients. That's the important thing.
Got it. Thank you.
Please stand by for our next question. Our next question comes from Greg Harrison with Bank of America. Your line is now open.
Hi there, this is Mary Kate on for Greg. Thanks for taking our question. I guess, regarding, Fabry, as you approach a Phase III trial, could you comment on the physician and patient advocacy interest in a gene therapy for Fabry and the impact of ERT freedom in this population? Maybe what is clinically meaningful here? Thank you.
Your line is hard to follow. Can I ask you just to repeat the crux of the question, please?
Yeah, absolutely. As you approach a Phase III trial, could you comment on the physician and patient advocacy interest in a gene therapy and also the impact of ERT freedom in this population?
Okay. Mark, I think this is maybe one for you.
Thanks for the question. First of all, I mean, just as a general rule, we actually engage with advocacy very early, actually prior to Phase I and work with them to provide input into our protocol designs, but also to better understand the patients. We also bring patients in to speak to us, to share their disease so that our scientists and researchers and developers actually can really understand what the patient requirements are. That's something that we're particularly proud of, and I think, you know, based on my experience, Sangamo does incredibly well. You know, in terms of, you know, next steps, we'll provide next steps, you know, at the appropriate time. I think that, you know, I think that we're making great progress with the program.
I think it's important that we, you know, finalize the details of that, and then we can provide the appropriate guidance to you later.
Thank you.
Please stand by for our next question. Our next question is from Kaelen Brizendine with Stifel. Your line is now open.
Hi. Thanks for taking the call. Our questions. This is Kaelen Brizendine on for Benjamin Burnett. I just had one quick question actually regarding some of your preclinical programs in brain disorders, such as the prion disease, tau therapies, Huntington's. I was wondering if you could talk about these a little bit in more detail, and just maybe when you'll be seeing these maturing into the clinical phase. Thank you.
Thank you for your question. We would love to share more about them. Unfortunately, in these partnerships, the communication on those is controlled by the partners. But what I would want to reassure you is the people around the table here sit on steering committees, development committees, research committees with the partners, and they're moving forward. We almost have a hidden early portfolio that is in our partner's hands. They're passionate about them. They love the science of Sangamo, and we hope to be able to say more soon as they get through the milestones and towards the clinic. Did you also ask about Prion? Jason, I know how excited you are about the Prion results. Can you touch on that? Because I think it is a remarkable piece of science.
Yes. Thanks, Andy. Yeah. One of our scientists, Bryan Zeitler, from Sangamo, presented at Prion 2020 earlier this year data that Sangamo has generated in collaboration with the Broad Institute at the Massachusetts Institute of Technology, where we were studying the ability of our zinc finger transcriptional repressors to be delivered to the brain of mice in a mouse model of prion disease and repress the expression of prion protein and thus prevent the spread of prion disease. The data that was generated there was really remarkable compared to control and compared to other approaches that we've known have been tried in similar models such as the ASOs.
The ability of the zinc finger transcriptional repressors to potently repress prion protein expression and dramatically extend the life of the mice in this mouse model of prion disease were very impressive. Several key opinion leaders in the field, international experts in prion disease, made comments about how impressed they were with the data. I think, there was even one comment that it was the most exciting data of the conference. This is a program that we're very excited about. It's a wholly owned internal program, and we are exploring moving it forward into humans as soon as we can. Of course, there are additional complications.
This was mouse data, and now we're dealing with the next steps to put together a package that would allow us to move it forward into an IND for testing in humans if possible.
Great. Thanks.
Please stand by for our next question. Our next question comes from Ritu Baral with Cowen. Your line is now open.
Good afternoon, guys. Thanks for taking the question. I wanted to ask about the profile of the female Fabry patients that you guys enrolled. Are they on the full ERT dose? I'm wondering about their kidney versus potential cardiac involvement or aspects of their disease. Further, in this expansion cohort, is there a target number of female patients that you're looking to enroll to inform the Phase III? Then I've got a follow-up.
Thank you, and thank you for your question. Yeah, it's exciting. We've moved into female patients. Bettina, can you give any more color on them?
Yes. For sure, I mean, what we have done in terms of the patient characteristics, you can see that data. There, there's a lot of detail in our ESGCT slides. We have patients with various characteristics. We do plan, and the protocol allows up to 30 patients to be dosed as part of the expansion phase, and that includes both males and females. It also includes a renal cohort, a cardiac cohort. We're not guiding at this moment as to the details of how many patients we have or plan to have in those specific cohorts, but we'll be making an update in early 2023 around that.
Bettina, I hope I'm not misspeaking here, but there are five different cohort, potentially five different cohorts?
That's right. I think we presented that at ESGCT. We have one cohort with antibody positive patients, another one with antibody negative patients. Another cohort is female patients, another one is a renal cohort, and another one is a cardiac cohort. Of course, these latter two cohorts can include both male or female patients.
Male and female. The females could be that cohort plus females with other forms of the disease.
Absolutely.
Does that help?
It does. That's helpful. Thank you. Then can you guys comment on where you stand on CMC for commercial product for the potential launch of that pivotal Fabry, especially on things that, you know, have tripped up other sponsors, assays, validation of assays, potency assays, all that sort of thing.
We take that part of development as seriously as we do the clinical piece. I know the clinical piece. I'm glad you've asked that because I know the clinical piece gets the most airtime and excitement. The only way to develop these medicine is paying attention to the CMC and the manufacturing. We're very under control. We have everything set up to go for both the Phase III and commercial.
Got it. Can I squeeze one last question in? Can you elaborate, Sandy, a little bit on the biopsy schedule, for patients in the expansion cohort?
Bettina.
Absolutely. For patients in the expansion cohort. Well, first of all, we do have two patients from cohort 4 who are naive patients for whom we have collected biopsy data. Those are the earliest patients with bilateral kidney biopsy data. We plan to share that information in early 2023. We are collecting kidney biopsies also for patients who are naive or pseudo-naive in the expansion cohort. That data will read out as the study progresses.
We're very grateful to the patients for volunteering to have kidney biopsies. Kidney biopsies are not a minor thing to have.
Mm-hmm.
To have the patient have both their entry biopsy and then to come back later for another one reminds us of our gratitude to patients and what they do to make these, this drug development possible.
Are these 12-month biopsies or 18-month biopsies?
These are six-month biopsies.
Okay. Got it. Thank you.
Please stand by for our next question. Our next question comes from Patrick Trucchio with H.C. Wainwright & Co Your line is now open.
Hi. Good afternoon. Just a couple of follow-ups. Just the first one is on the Fabry program. I'm wondering if you can discuss in more detail the safety and tolerability profile that you've seen so far in the program. If you can talk more specifically, what it is about it that has enabled you to avoid some of the side effects and adverse events that we've seen with some of these other programs in the space. To what extent could these learnings be applied to current or future gene therapy or editing programs in development from the platform?
Thanks for your question. Bettina, you don't really have much to say about the safety profile, do you?
Which is good. Thank you, Sandy. Yes. On the safety and tolerability side, as you've seen, we are doing extremely well. The patients are doing extremely well. We have not needed to treat any of the patients with steroids reactively. Patients are not treated with steroids prophylactically. We continue to monitor patients, and as I mentioned earlier, we now have seven patients dosed at the highest dose cohort. It's a question of monitoring these patients and the next patients. I think what the clinical trial team has really been doing well is paying a lot of attention to the details around education and around the infusion schedule. We're very pleased with that, with the progress on the safety and tolerability side.
We've used AAV6 now across the MPS trials, the hemophilia trials, and now Fabry. We've got quite a broad patient experience, and it is remarkably well tolerated even at 5e13. The only thing that we saw or we have seen in the hemophilia trial is occasional LFT events that are resolved quickly and easily with steroids. What's interesting is that we haven't seen any of these thus far in the Fabry trial. The question must be why is that? The truth is that we don't have enough experience yet, enough patients followed to understand why it is that the cargo seems to make some kind of difference in this.
Yeah, that's helpful. Then just on the preclinical pipeline, just following up on some of the discussion earlier. You know, there's many preclinical programs in the areas of CAR T-reg cell therapies, you know, for autoimmune disorder and as well gene editing for neurological disease and many indications, both internal and externally with partners. I'm wondering if you could frame for us which program or programs do you think are perhaps not as well appreciated as some of these more advanced clinical programs? When we can expect some of the next updates on those for some of these underappreciated programs?
Thank you. Jason, you're very excited by the CAR-Treg programs and the CNS. Can you say which ones you particularly would want to highlight?
Well, thanks, Sandy. In the CAR-Treg space, we've discussed the programs that we're moving forward in the preclinical space in multiple sclerosis and inflammatory bowel disease. We believe that both of those areas are great opportunities for the therapeutic use of T-regs. Really, I'm excited about the advancement of both of those. You know, regulatory T-cells offer the potential to kind of transform the treatment of autoimmune disease by targeting immune regulation to a specific tissue, for example, in the CNS for multiple sclerosis. The ability to offer a durable long-term benefit to patients rather than constantly being treated with a medication for the lifetime of a disease. It's really a
You know, the way we view the CAR-Treg platform is something that has the potential to transform the treatment of autoimmune disease, and we're very excited about those programs moving forward. In the CNS space, I'd say what's most exciting is, you know, is the diversity of the pipeline. You know, we have our zinc finger transcriptional regulators, which just as a reminder, can either upregulate or downregulate genes. Those are being used in our collaboration with Biogen and our collaboration with Novartis in neurodegenerative diseases and neurodevelopmental diseases, respectively. We're very excited about the progress that's being made there. Our partners are really excited. I think the fact that those partnerships and those companies came to Sangamo acknowledges the amazing toolkit that we have.
We're also advancing our own internal programs, and Prion was highlighted, and we have several other non-disclosed programs that we're looking forward to share data with at the appropriate time. On top of that, an area that I'm probably most excited about in the last year is the advances that we've made in our AAV capsid engineering work. We have a very healthy effort in developing new AAV capsids that can deliver our zinc finger tools to the CNS, either by direct injection or via the blood or across the blood-brain barrier. We've made some remarkable advances there. Some of that data was presented at ASGCT earlier this year.
The teams that are doing that work, those directed evolution studies to identify new capsids that are even more effective, have been continuing to generate exciting results. With those capsids, it's gonna open up even more indication space to go after more and more diseases. Because at the moment, really, the zinc fingers are working amazingly well, and it's really a matter of getting those tools to the right cells in the body and getting the coverage that's necessary. That's what the new AAV capsids that we're developing will afford. We're super excited about that work as well.
That's helpful. Thank you very much.
At this time, I would now like to turn it back to Louise Wilkie for closing remarks.
Thank you. Thanks once again for joining us today and for everyone's 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. Thank you.
Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.