Thank you for standing by, and welcome to Sangamo First Quarter 2022 Teleconference Call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions] I would now like to hand the conference over to your speaker today, Ms. Louise Wilkie. Thank you. Please go ahead. .

Good afternoon, and thank you for joining us today. With me on the call this afternoon are 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 related to the therapeutic and commercial potential of our product candidates.

The anticipated plans and time lines of Sangamo and our collaborators for initiating and conducting clinical trials and presenting clinical data, execution of our corporate strategy, advancement of our product candidates, our 2022 financial guidance 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 on our quarterly report on Form 10-Q for the fiscal quarter ended March 31, 2022, and our annual report on Form 10-K for the fiscal year ended December 31, 2021.

The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information, except as required by law. On this call, we discuss our non-GAAP operating expenses. Reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website.

Now, I'd like to turn the call over to our CEO, Sandy Macrae. .

Thank you, Louise, and good afternoon to everyone on the call. Building on a year of significant clinical and preclinical progress in 2021, Sangamo advanced multiple programs in the first quarter of 2022 as we continue our mission to create transformative genomic medicines for patients using our innovative technologies.

We are proud to have 3 programs progressing towards or in late-stage development and to be the first company known to us to dose a patient in what we believe is a completely new treatment modality. This quarter, we dosed 3 additional patients in our differentiated and wholly owned gene therapy program for the treatment of adults with Fabry disease.

We have now successfully dosed a total of 9 patients across 4 cohorts in the STAAR Study to complete the dose escalation portion of the Phase I/II study. We are delighted to have achieved this significant milestone.

And with recent changes in the competitive landscape continue to believe that we are in a leading position amongst gene therapies for Fabry disease. We look forward to presenting updated data in the second half of '22.

We and Sanofi dose of this patient in the Phase I/II PRECIZN-1 study, our zinc finger nucleus modified autologous cell therapy for the treatment of sickle cell disease. We expect to complete patient dosing in the third quarter of 2022 and look forward to sharing an update on data in the second half of this year.

Regarding the Phase III Hemophilia A Gene Therapy trial, Pfizer announced that in March, the FDA lifted the clinical hold that have been placed on their fine trial. Pfizer announced that dosing will resume once all necessary conditions are met, including approval of updated trial protocols by regulatory authorities.

Pfizer anticipates resuming the trial in the third quarter of '22, with a pivotal data readout estimated in the second half of 2023.

In March, Sangamo dosed the first patient in our Phase I/II STEADFAST clinical study evaluating TX200, our wholly owned autologous CAR-Tregs cell therapy product candidate for the prevention of immune-mediated rejection in HLA-A2 mismatch kidney transplantation from a living donor.

We are thrilled to have achieved this momentous milestone, which we believe is the first in human dosing of an engineered CAR-Tregs cell therapy candidate. Most importantly, the patient continues to be well and has not reported any adverse events related to the treatment to date.

We are planning to dose the second patient in the STEADFAST study around the middle of '22. Based on their transplant schedule and looking forward to sharing the appropriate data at the right time.

Before Rob provides more detail on these programs, I want to note that these advancements have resulted from our strategic and focused use of research and development capabilities, which are supported by our in-house infrastructure, including AAV and cell therapy manufacturing facilities.

We believe that this positions us well to create new transformative medicines for patients in need and to generate long-term value for our shareholders. With that, I'd like to head over -- turn over the call to our Head of Development, Rob Schott, who will outline the progress of our clinical programs in more detail.

Rob?.

Thank you, Sandy, and good afternoon to everyone on the call. Our development organization remains focused on execution in the clinic, and we are pleased with this quarter's progress.

Beginning with our Phase I/II STAAR study examining isaralgagene civaparvovec, or ST-920, which is our wholly owned gene therapy program for the treatment of Fabry Disease in adults. This quarter, the Safety Monitoring Committee approved escalating to a fourth dose cohort as outlined in the STAAR study protocol.

This was based on the totality of data from the previously dosed patients. 2 patients have since been dosed in cohort 4 at the 5e13 vector genomes per kilogram dose level, completing the dose escalation portion of the Phase I/II study. Furthermore, this quarter, we dosed an additional patient in cohort 3.

This achieves a total of 3 patients in this cohort in 9 patients overall that have been dosed in the STAAR study to date. In addition, during this quarter, we completed withdrawal of enzyme replacement therapy from a second patient, which means that we now have withdrawn on each from the first and second cohorts.

These patients are being closely monitored and investigators have thus far not deemed it necessary to resume enzyme replacement therapy. We expect to provide updated results from the STAAR study in the second half of 2022 and are actively preparing for both the Phase I/II expansion cohorts in a Phase III clinical trial.

In the Phase I/II PRECIZN-1 study of SAR445136 for the treatment of sickle cell disease. This quarter, we dosed the fifth patient.

This patient was the first in the study to receive a product candidate manufactured using improved methods that have been shown in internal experiments to increase the number of long-term progenitor cells in the final product. We expect to dose the remaining patients in the study in the third quarter of this year.

We look forward to sharing an update on the PRECIZN-1 study in the second half of 2022. Feedback has been received from the FDA and Phase III enabling activities, including manufacturing readiness are in progress.

The orderly transition of Sanofi's rights and obligations under this program back to Sangamo is progressing well and is on track to be completed on June 28. As previously outlined, Sangamo is excited to have this asset back in our hands soon.

As Sandy outlined in his opening, Pfizer recently announced that in March of this year, the FDA lifted its clinical hold on the Phase III AFFINE trial, evaluating giroctocogene fitelparvovec, an investigational gene therapy for hemophilia A.

The hold was put in place following the observance of Factor VIII expression levels greater than 150% in some treated participants. Pfizer has announced that the voluntary pause remains in place until all necessary conditions are met, including approval of an updated drought protocols by regulatory authorities.

In addition, Pfizer was made aware of a below-the-knee deep veins thrombosis in 1 participant with elevated Factor VIII levels. This patient had a history of thrombotic events prior to participation in the trial, which is a known risk factor for subsequent events and an exclusion criterion for participation in the AFFINE trial.

The case was assessed to understand all potential contributing factors, including mix doses of investigator prescribed direct oral anticoagulants. The patient is reported to be doing well. All study participants continue to be closely monitored and there have been no other thrombotic events reported in the study at this time.

The information was shared with study investigators, health authorities and the independent external data monitoring committee and Pfizer responded to queries from health authorities.

Pfizer and Sangamo remain committed to the hemophilia community and Pfizer anticipates resuming the trial in the third quarter of 2022 with a pivotal data readout estimated in the second half of 2023.

In the first quarter, Sangamo also had significant and trailblazing development on our wholly owned TX200 CAR-Tregs cell therapy candidate for the prevention of immune-mediated rejection in HLA-A2 mismatch kidney transplantation from a living donor.

On March 22, we dosed the first patient in our Phase I/II STEADFAST clinical study in what we believe is the first ever dosing of a human with a CAR-Tregs cell therapy candidate. Continuing Sangamo's track record of advancing groundbreaking therapies in genomic medicine.

The patient continues to do well following dosing with the Autologous CAR-Tregs therapy and has not reported any adverse events related to the treatment to date. As you know, safety and tolerability continue to be among the major goals of the Phase I/II study.

TX200 was designed with the potential to prevent kidney rejection by reducing local inflammation and promoting immunological tolerance to the graft.

This investigational cell therapy is composed of Autologous CAR-Tregs cell engineered to express an HLA-A2, CAR and is being assessed in the HLA-A2-negative patients receiving a mismatched HLA-A2-positive kidney from a living donor. TX200 Engineer CAR-Tregs are expected to localize to the graft and activate upon binding the HLA-A2 antigen.

Through their ability to regulate the immune system, TX200 cells may protect the graft for immune-mediated rejection and reduce or eliminate the need for lifelong treatment with immunosuppressants.

In the STEADFAST clinical study design, each patient undergoes a leukapheresis procedure to collect their white blood cells, which after Tregs cells are isolated are genetically engineered and in cryopreserved. The patient subsequently undergoes transplantation surgery to receive a kidney from a living donor.

Following a recovery period, the patient receives their individualized TX200 investigational cell therapy. Dosing of patients, therefore, occur several months after patient enrollment.

Secondary objectives include the incidence of biopsy confirmed acute graft rejection, incidents of chronic graft rejection and confirmation that TX200 CAR-Tregs cells localized to the transplant of kidney. We also plan to evaluate the ability to reduce systemic immunosuppressive therapy, which carries the risk of significant systemic toxicity.

Sangamo expects to dose a second patient in the STEADFAST study around the middle of 2022 based on their transplant schedule, and we plan to complete the first cohort, which comprises a total of 3 patients by the end of the year. We look forward to sharing data at the appropriate time.

We see this study as the first step in our R&D journey towards a potential pipeline of CAR-Tregs therapies for autoimmune diseases. In addition to TX200, Sangamo is developing CAR-Tregs cell therapy candidates in preclinical studies, including for potential use in treating multiple sclerosis and inflammatory bowel disorders.

I will now turn the call over to our Chief Scientific Officer, Jason Fontenot, for an update on our preclinical programs.

Jason?.

Thank you, Rob, and good afternoon, everyone. We continue to make strong progress across a range of preclinical programs based on our cutting-edge genomic engineering platform.

We're particularly pleased to recently announce Sangamo's significant presence at the upcoming American Society of Gene and Cell Therapy, ASGCT, Annual Meeting in Washington, D.C., which takes place later this month. We look forward to presenting a total of 8 abstracts across 3 key areas.

Firstly, we will show the latest innovations in our genomic engineering platform, including our base editing program and the use of zinc finger transcription factors for multiplex engineering of CAR-Tregs cells without changes to the genetic code.

Secondly, we will highlight important advances in our AAV Capsida Engineering Program, a critical component of our CNS focus in vivo genome engineering portfolio. And finally, our CAR-Tregs cell therapy platform, including presentations on our TX200 program and a presentation on our preclinical allogeneic Treg engineering program.

For the full list of Sangamo abstracts accepted at ASGCT, please see the press release we issued earlier this week, which is available on the Media and Investors page of our website. These abstracts are representative of a robust Sangamo research engine and our continuous drive to innovate and evolve our genomic engineering platform.

I'm privileged to work with the dedicated team responsible for this work. Worked as the backbone of saying most strong long-term pipeline that we believe can deliver innovative medicines to patients in need. I will now turn the call over to Prathyusha for an overview of our financial results.

Prathyusha?.

Thank you, Jason, and good afternoon, everyone. Our financial results for this quarter are available in the press release issued this afternoon, which can be found on our website.

This quarter, we continued to build on our 2021 investments, including advancement of our clinical programs, our preclinical research pipeline and optimization of our in-house manufacturing capabilities. We ended the quarter with approximately $400 million in cash, cash equivalents and marketable securities.

We believe that our balance sheet remains strong for continued execution across our expected upcoming key cases. Turning to 2022 full year guidance. Our 2020 to full year non-GAAP operating expenses continues to be expected to be between $280 million to $310 million for the year.

This range excludes estimated noncash stock-based compensation expense of approximately $40 million. We expect a significant portion of our operating expenses to be invested in continued progress of Elite programs, including Fabry Phase III planning activities, Phase I/II activity for TX200 and preclinical work in CAR-Tregs and CNS indications.

We also expect to grow our investments in sickle cell disease in the second half of the year following the transfer of the program back to Sangamo. I'll now turn it back to Sandy for closing remarks. .

Thank you, Prathyusha. When we last spoke in Fabry, I said our accomplishments in 2021 would set us up for a strong 2022. And I believe our momentum in the first quarter bears this out. We are a fully integrated genomic medicine company, building momentum with our novel science, clinical execution and in-house manufacturing.

The first quarter progress we have outlined demonstrates how this is coming together to create hope amongst the patients we're working to serve, a significant opportunity for our company and the potential for long-term sustainable value for our shareholders.

I'm very grateful to my leadership team and all my Sangamo colleagues for their dedication to and hard work towards our mission of creating new transformational genomic medicines for patients.

We look forward to expected key milestones and catalysts throughout the year, including presentation of additional Phase I/II STAAR data for Fabry disease as well as the dosing of patients in the expansion cohorts.

Dosing of the remaining patients in our Phase I/II PRECIZN-1 study for sickle cell disease along with presentation of additional data from this study. Dosing of additional patients in our Phase I/II TX200 CAR-Tregs STEADFAST study and Pfizer's potential resumption of the pivotal Phase III AFFINE trial in hemophilia A.

Operator, please open the line for questions. .

[Operator Instructions] Our first question comes from the line of Yanan Zhu from Wells Fargo..

Hi, thanks for taking my questions and congrats on the progress this quarter. I have a few questions, but they are relatively quick ones. On Fabry's program, it sounds like 2 patients have been off ERT.

Congratulations on that finding? And could you share the duration for either both or the longer patients? And also, what is the criteria for restarting ERT? Is it like a lyso-Gb3 level at baseline? Or is it a specific life or Gb3 level? And then on the program, I have a very quick question, whether that case has been communicated with regulators? And then I have one question on the base editor program.

.

Thank you. Lots of great questions. So I'm going to distribute them here. And so Bettina will take on the Fabry question. Jason will talk to you about base editors. And just to give a quick answer for the hemophilia A program, yes, Pfizer reported this immediately to the regulatory authorities. And it happened about the same time as the clinical hold.

So it's been with all of the regulatory authorities for some period of time. So Bettina, over to you. .

Thank you, Sandy. So thank you also for the question. For Fabry, we're obviously very excited to have now those line patients in the study. And as far as those 2 patients who have come off ERT, the first one we had already announced at the World Conference in February. So this patient has been off ERT for several months now.

The patient came off ERT towards the end of last year. And the second patient came off ERT just a few weeks ago. So he's been off ERT. And in terms of whether and when the patients would resume ERT, really, we are looking at this together with the PIs in terms of all the data coming out. It's not just the biomarkers, the clinical picture.

It's a conversation. Right now, there is no indication that ERT withdrawal would be necessary in either of these patients. .

You mean they don't need to go back on to ERT. .

Correct. .

Okay. Thank you, Bettina. Jason, can you help with some comments about the base editor? I know you're very excited about it. .

Yes, I'm happy to.

What is the specific question?.

Right. So yes, so we see that you have an abstract at ASGCT. You have a zinc finger-based base editor. Obviously, many, many questions, very much looking forward to the presentation such as questions such as how you enable the AAV capability there, how you put everything into one vector.

But I guess I'll just ask the kind of most interesting question in my -- from my perspective, that is with this kind of finger-based totally novel architecture.

Do you still have this phenomenon of by standard editing? And how does that compare with the base editor that is already out there?.

Yes. So thank you for the question. Yes, we are -- we have a group of world-class structural biologists and molecular biologists on the Sangamo team, and we're continuously pushing to innovate our platform to develop new functionalities for our genomic medicines toolkit. The latest one that we're presenting at ASGCT is our base editor.

I think for the really specific details, it's best that you engage with the scientists that are presenting the work and look at the work. But we're tremendously excited about it.

And I think what's most notable about it are one of the many notable things about the work that we're putting together is how -- because we're leveraging our zinc finger technology, we're able to construct a compact base editor that we can deliver with an AAV vector, which we think is pretty exciting.

But it can also be used in with other delivery modalities. So I think we've got something that it's just another tool in our kit and there are places where using base editors is particularly attractive, especially in the multiplex editing of cells ex vivo, but there are other in vivo applications that we're excited about.

And yes, I look forward to everyone being able to see the data and talk with our scientists. And obviously, we have a publication on this in the works and that will be another great time to learn more of the details. .

Thank you, Jason. Just to be clear, the construct is small if you can go into a single AAV. It doesn't have to be broken up as other versions of this. .

Correct. That's correct, Sandy. .

Great. Thank for the color. .

Thank you for your questions. .

The next question comes from the line of Nicole Germino from Truist Securities..

Thanks for taking my questions and congratulations on the progress. Given that earlier this week, Vertex had a clinical hold that it may be that there are some questions that FDA has before the company can generate more data.

Are you anticipating delays or questions from health authorities in Europe or from FDA during the dose escalation phase of the STEADFAST program. And given that the company is a pioneer in the CAR-Tregs space with this first in-human study. And I only see European sites on the clinicaltrial.gov. Will there be U.S.

sites coming online in the near term? And I have one quick follow-up. .

Well, can I hand this one on to Rob, our Head of Development, who's been working very closely with our friends and Pfizer.

Rob?.

I saw the VERTEX data and indeed, they had a clinical hold, that's a cell therapy for diabetes. We have been interacting regularly with regulators in Europe to ensure that we can proceed through our dose escalation for TX200 without any anticipated clinicals being placed on the program to answer that question.

I hope does that answer your question with respect to that. I think the key to that is regulatory interactions on the whole way -- what additional breaking down from the... .

Sure. The other part of it was on clinicaltrials.gov, I only saw European sites, clinical sites. Are there going to be any U.S. sites in the near term that are coming on in... .

We have, I think, for the first -- for the dose escalation, we're going to be at European sites. We have several sites that are signed on, and we think we're going to be able to escalate successfully this year through our European colleagues. .

Got it. And then my quick follow-up is just beyond renal transplant, will conditioning be required for CAR-Tregs therapies in other chronic disease indications in either autologous or allogeneic setting. .

Well, depending on the cell therapy, preconditioning is required for, I think, everything that's been required preparation of bone marrow for the engraftment. I don't know of any examples where preconditioning has not been used. There are a number of preconditioning protocols.

So there's constant work to reduce the patient burden with respect to that preconditioning but in order to ensure adequate engraftment, typically, these are being used. .

Great. Thank you so much..

The next question comes from the line of Luca Issi from RBC Capital. .

Good morning, guys, and thanks for taking my questions. Congrats on the progress. I have 2 quick ones. Maybe on Fabry, obviously, very impressive serum biochemical response here, but wondering what's the plan on actual kidney biopsy.

Would you look at kidney biopsy directing Phase III or we look at them in the expansion cohort of trial? Any call there would be great. And then maybe circling back on hemophilia A, just to be clear, was the event of deep veins thrombosis reported before or after the clinical hold was lifted.

In other words, did the FDA list the clinic whole fully aware of this event? Or was that not the case? Thanks so much..

Thank you for your question. So Bettina taking the questions for Fabry disease.

So Bettina, please?.

Yes. So thank you for the question. So as far as kidney biopsies are concerned, we have now started doing kidney biopsies in the cohort 4 patients, the 2 cohort 4 patients that we have enrolled and dosed. These are 2 naive patients.

And as such, kidney biopsies are a good setting for these patients, and we will continue to do so in naive pseudo naive patients going forward regardless of whether of which part of the study that had is in. .

Thank you, Bettina.

Rob, can you help us with the timing of the clinical hold and the DVT patients?.

Yes. So just to set the time line, the Pfizer Institute of voluntary hold, and then this was followed shortly after by a clinical hold by the FDA. Then the DVT occurred, and there was no additional regulatory response after the DVT.

We've disclosed that the patient had been enrolled in the trial despite a history of prior DVT, which would be exclusionary normally. But the clinical hold was lifted with that knowledge of a DVT and Pfizer, as we've announced this plan to resume the trial likely in the third quarter of 2022. .

Super helpful. And if I may, why was that patient enrolled in the first place? It looks like that was a patient that was supposed to be excluded. So wondering if you have any color on that. Thank you so much..

I don't have insight into that particular protocol violation, but the patient was indeed enrolled with knowledge of a prior DVT. My understanding, understanding this came after all the events were disclosed. .

And you can be certain that the investigators are now reminded that they shouldn't enroll patients with a previous history of DVTs. And I'm sure the label will reflect this once the drug is available in the market. .

Got it, thanks so much guys. Very helpful. .

The next question comes from the line of Ben Burnett from Stifel. .

Hi, this is Kelly O'Brien on for Ben Burnett. Thanks for taking the questions. I guess really fast maybe following up a little bit on a prior question.

But regarding the Fabry disease program, can you give us a sense of the range of follow-up time that the patients in the trial currently have, including both the ones previously on ERT and the ones who are naive. And then maybe how much follow-up time we could expect to see at the update that's expected in the second half of 2022. Thank you..

Certainly, we're happy to do that.

Bettina, can you give some color to that?.

Yes, absolutely. So we presented our Fabry data for the first few patients at World this year. And the patient -- the first patients were enrolled approximately more than -- definitely more than a year ago. The first 2 or 3 patients are now in the follow-up study, which means they are beyond 1 year follow-up.

So up to around 15 or 18 months of follow-up for the first patient and the last 2 patients or the patients enrolled in cohort 4.

So for cohort 4, the last patient has approximately 4 weeks, I would say, of follow-up, and we anticipate that data for these 9 patients, in particular, for the cohort 4 patients to be reviewed at an upcoming safety monitoring community meeting, and we plan to then share data at an upcoming meeting likely in early or later in this year. .

And the thing that's been most impressive between has been how sustained the levels of alpha-Gal have been in both patients on ERT and patients that are not near 2. .

Exactly. We're very pleased with the -- especially with the alpha-gal enzyme activity levels for these patients. And in fact, the safety and tolerability, as we've gone through this thoughtful dose escalation process has been very, very comforting. And so we look forward to sharing all of that data later this year. .

Okay, thank you for the color. If you could also -- just a quick question on the sickle cell disease program. I know you dosed the fifth patient with an improved manufacturing method. I was wondering if you could elaborate a little bit exactly what those improved methods were at all. Thank you. .

We haven't been talking about that. We're very pleased that our friends at Sanofi had been working on that for some period of time now. And so this new patient is the new manufacturing method. So we're very careful that it's not a sufficient change to make it a new product.

But it maximizes the chance of long-term progenitors, which we think are essential for the engraftment and the production of hemoglobin F in the prevention of sickling events. .

Awesome. Thank you so much for the question. .

Next question comes from the line of Greg Harrison from Bank of America. .

Great, thanks for taking my questions. On sickle cell program, what factors are driving your decision process on the future of this asset as you move forward, either on your own or with the new partner.

Where do you see the points of differentiation for your product?.

Mark, can you take this one?.

Sure. Yes. So obviously, our first priority right now is to complete the Phase I/II PRECIZN trial to try to get a sense of whether the new manufacturing process indeed has an effect on the clinical results. Obviously, we're cognizant that the competitors, including CRISPR, Vertex are guiding in terms of when they're planning on filing.

We will basically take a look at the program if we feel it's competitive, then we will either advance that ourselves or look for someone to advance the program with if we feel that, that increases the likelihood that we would be able to get that to patients earlier.

I think one thing to keep in mind with sickle cell disease is that there's about 100,000 patients in the United States, of which 20,000 to 30,000 are severe.

If you take a look at the ability to service patients with these cell personalized cell therapies, effectively, you're limited in terms of your ability to reach patients based on your manufacturing capacity.

And so we believe if we've got a competitive profile or if the data suggests we've got an improved profile, then there's an opportunity to service that important disease area, and we'll provide the appropriate updates on our plans when we get there. .

Great, that’s helpful. Thanks..

The next question comes from the line of Gena Wang from Barclays. .

Hi, good afternoon, this is Harshita on for Gena. Thank you so much for taking my questions. I had 2 on ASGCT.

So the first one, again, on the zinc finger architecture for high-efficiency based editing, I think in your abstracts, you noted exploring the M&As domain from other bacterial toxins to improve performance and that one domain led to 60% editing in human T cells.

I was curious as to if you could disclose at this point how many DMAs domains you explored and what was the general range of editing you observed? And the second is a quick clarification. For the CAR-Tregs program, on STEADFAST, there was a poster that you'll be presenting at ASGCT.

Is this on trial design? Or can we see -- are we going to see data from the first patient from your prepared remarks, I'm guessing not, but just wanted to confirm. Thank you so much. .

Okay. Jason, just before we go to that, Louise, can you say about the Treg [ph]..

So the STEADFAST post that we'll be presenting at ASGCT is a trial in progress poster we will not be sharing any clinical data coming from that trial at ASGCT. .

Jason, can you say something about base editing, please?.

Yes. So on the question of the different domains that we explored, we explored a number of domains, I would say, probably over 20%.

I'm not going to get into the details on that right now, but the team did an incredible job of mining the known perigonium for potential deaminases and we've identified one that is particularly active and effective as a therapeutic. So that's the one that we've moved forward.

And we believe it has all of the qualities necessary to deliver therapeutic grade base editing in the context of our zinc finger architecture, which, as we went over early allows us to design a base editor that is highly compact and capable of being delivered by a single AAV and also obviously useful for ex vivo engineering or any other delivery platform.

.

Great. Thank you so much..

Thank you for your questions. The next question comes from the line of Marie Hoff from Jefferies. .

This is Kevin on for Maury. Just a quick couple of questions. First, on the TX200 patient.

Can you say how that patient is doing and potentially whether you're getting any Tregs persistent expansion? And then could you talk more about how often you're assessing blood biomarkers and what will drive your decision-making process to reduce immune suppressants. .

There's very little I can say at the moment. The patient is doing well. We haven't given any indication yet when we're going to talk about the -- any biopsy data or any biomarker data. So it's early days in this study, and we look forward to sharing that later in this year, probably more likely at the beginning of next year. .

Okay. Great. That was actually my follow-up, if we could potentially see data by the end of this year and then -- and what might be included in that data update? And then if you could talk about what's guiding your higher or alternative dosing strategies. .

So I think you should expect beginning of next year for the data. And if it comes sooner, that would be a bonus.

We've already planned the number of cells for low, medium and high doses, and we'll be looking to see the -- from the very first dose because these cells when they go to the -- when they find the antigen and are activated, they -- our hope is they expand. So any one of the doses could have a therapeutic effect.

So this is a trial where we'll be watching and learning as we go. .

Great, thanks..

The next question comes from the line of Ritu Baral from Cowen. .

Good afternoon, guys. Thanks for taking the questions.

Sandy, have you confirmed that cohort 4 in the Fabry trial is going to be the expansion cohort? And I guess if that's still TBD, how much follow-up do you need from cohort 3 and cohort 4? And do you need biopsy data from cohort 4 to make that final determination of what is going into the expansion cohort. .

Bettina, can you take that one. .

Absolutely. Thank you, Sandy. So cohort 4 is our final cohort for the dose escalation phase. We have dosed cohort 4 at 5e13, the protocol allowed for us to reach this dose, and that was based on the safety and tolerability profile. As I mentioned earlier, we will be holding a safety monitoring committee meeting. This will be held by Q3.

And at that point in time, all of the data that we have until that point will be used to assess our next steps into the best way forward for our expansion phase. And we intend to dose patients in the expansion phase as soon as we help as we as we gather the safety monitoring committee and make that decision to move forward.

So there won't be any biopsy data. We only have baseline biopsy data at this point in time for cohort 4, and the data will be based on safety, tolerability and biomarker data. .

Absolutely. .

Point?.

We've been very lucky to have efficacy from the first dose in this and across each one of the doses. So we're -- it's an important decision to make. It will be based understanding the tolerability and maximizing the chance of efficacy. .

What time points for the biopsies are you going to look at?.

We look at baseline in 6 months. And so you can expect that we won't have any biopsy data this year, we'll have biopsy data likely towards the -- to share towards the beginning of next year. .

Got it.

And when do you plan on taking CMC all the way up to commercial product? Do you expect to enter the expansion cohort with commercial-grade product? Or will that be for a separate pivotal?.

So we are in plans to transition to the commercial manufacturing, but we're not guiding on which we're going to use for the expansion cohort right now. But obviously, where it becomes very important for us is to make sure that we've got the commercial production facility ready for enrolling the Phase III program.

And that way, we've got a consistent Phase III with our commercialization line. .

Got it. And flipping back to PRECIZN and the sickle cell program, the CMC, you did mention that Phase II readiness activities are in progress and you've got the, I guess, the tech transfer from Sanofi occurring with their optimized program.

When all that is said and done, will you be a commercial-grade product for the SCD program? Or will there be further work to be done?.

So we expect to do the tech transfer and be Phase III ready as part of the preparation for the Phase III plan. .

And Phase III would be run with commercial products.

Correct?.

Correct. .

Great. Thanks for taking my questions..

Thank you..

The next question comes from the line of Patrick Trucchio from HC Wainwright. .

I just have a few follow-up questions actually on the CAR-Tregs platform.

So first, I'm wondering if you can discuss the status of the preclinical CAR-Treg cell therapy programs, specifically in IBD and MS and what the time line to an IND or CTA filing can look like for those programs? And then separately, what learnings, if any, have emerged so far from the TX200 program that could impact the IBD and MS programs?.

So I'm going to ask Jason to tell you about his passion for Tregs and the work that is done by our colleagues in Valban. We've only just dosed the first Greg patients, so there is no learnings yet that we can apply to the other programs, and we haven't guided on the IND timing.

So Jason, can you give some indication of the progress that you're seeing on the Treg programs. .

Yes. Thanks, Sandy. Yes. So we have very active preclinical programs for developing CAR-Tregs for both IBD and multiple sclerosis. We've disclosed that one of the core targets for the IBD programs is IL-23 receptor. And I believe that there was a poster presented on that topic. -- in -- at a conference in Europe recently.

So I would point you to that poster for details on the program. For the multiple sclerosis program, we have disclosed a CAR targeting mog protein that's restricted to the CNS. And work is proceeding on both of those preclinical work is proceeding on both of those programs.

We've built a great kind of engine to evaluate, to generate and evaluate CAR through an in vitro and in vivo screening funnel so that we have the optimal car that's designed specifically for working in regulatory T cells. And so that work is well underway, and we're now evaluating our car engineered Tregs in vivo models in both of those indications.

We're really excited about the work that we've done and the platform that we put in place.

And it's true that while we haven't learned anything from the patients that have been dosed with TX200, I will point out that the investments that we've made in process development and manufacturing as well as obviously the biological expertise of the team that's working on this.

We're all developed during the TX200 preclinical efforts and up all to this day, and all of that information is obviously feeding into both of those preclinical programs. So we're very excited about our progress.

And then the last thing I'll point out is that the other area that we're really invested in is leveraging our zinc finger genome engineering platform to develop allogeneic Tregs.

And we're doing that by both doing engineering of Tregs derived from healthy donors, so the so-called healthy donor route to autologous cell therapies, but we're also doing a lot of work to drive Tregs from iPSCs such that we can engineer induced potent stem cells to be allogeneic and have a kind of continuous perpetual source of Tregs for an off-the-shelf therapy.

So we've got a really active Tregs program platform program at the company and tremendous advance in getting the first patient dosed, and we look forward to telling you more about the latest developments when it's appropriate. .

That's really helpful. Thanks so much. .

There are no questions at this time. I'm now turning the call back to you, Louise Wilkie..

Thank you once again for joining us today and for your questions. We look forward to keeping you updated on our future developments. .

This concludes today's conference call. Thank you for participating. You may now disconnect..