Thank you all for standing by and welcome to the Sangamo Third Quarter of 2021 Teleconference Call. [Operator Instructions] Please also note that today's call is being recorded. I would now turn the call over to your host Aron Feingold, Head of Corporate Communications. Ma’am, you may now begin.

Good morning and thank you for joining us today. With me this morning on this call are several members of the Sangamo executive leadership team, including Sandy 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 on our website, sangamo.com, under the Investors and Media section under the Events and Presentations page. This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements relating to therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for conducting clinical trials and presenting clinical data, execution of our corporate strategy, advancement of our product candidate, our revised 2021 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 our annual report on Form 10-K for the fiscal year ended December 31, 2020, as supplemented by our quarterly report on Form 10-Q for the fiscal quarter year ended September 30, 2021. The forward-looking statements stated today are made as of this date and we undertake no duty to update such information, except as required by law. On this call we discuss our non-GAAP operating expenses. Reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website. Now, I'd like to turn the call over to our CEO, Sandy Macrae.

Thank you, Aron, and good morning to everyone on the call. This is such an important moment for Sangamo as we share clinical data and business updates across several programs demonstrating that we have three important assets in or progressing towards late stage development. Our gene therapy portfolio is advancing with accumulating safety and efficacy data in our Fabry and Hemophilia A programs. Additionally, we are delighted with the preliminary proof-of-concept data demonstrated the clinical potential of our genome engineering, zinc finger technology in sickle cell disease. This morning, we announced preliminary clinical data from our Phase 1/2 STAAR study, evaluating isaralgagene civaparvovec or ST-920, our Fabry disease gene therapy product candidate. Data from this important study were evaluated from the four patients in the first two cohorts. Those levels point 5e13 and 1e13 vg/kg as of the cutoff date September 17 of this year. These encouraging results showed that for the first four patients ST-920 was generally well tolerated. There were no treatment related adverse events higher than Grade 1, and no treatment related serious adverse events. No patient experienced liver enzyme elevations, or required steroid treatment. All four patients exhibited above normal alpha-Gal A activity, which were maintained for up to one year for the first patient treated and through 14 weeks for the most recently treated patients. Levels ranged from two to 15 fold above normal levels at last measurement as of the cutoff date. Interestingly, the first three patients dose reported improvements in ability to sweat a primary and common Fabry disease symptom that limits exercise tolerance for the patient. ERT withdrawal is now complete for one patient and is planned for the other patient on ERT based on the stability of their alpha-Gal A activity following treatment. Based on these data, we've initiated Phase 3…

Thank you, Sandy, and good morning. Our financial results for this quarter are available in the press release issued this morning, which can also be found on our website. I want to reiterate that this is an exciting moment for us as a company and this quarter, we continue to invest in the advancement of our clinical programs, including Fabry and TX200, our pre-clinical research pipeline and our in-house manufacturing capabilities. With approximately $519 million in cash, cash equivalents and marketable securities at the end of the quarter, we believe that our balance sheet remains strong. Turning to 2021 full year guidance. We expect non-GAAP operating expenses to be between $265 million to $275 million for the year, which is within the range of the guidance that we have previously provided. This range excludes estimated non cash stock-based compensation expense of approximately $35 million. I will now turn the call back to Sandy for closing remarks.

Thank you, Prathyusha. We are very excited about these clinical data readouts. We show the advancement of our first generation genomic medicine pipeline with traditional gene therapy and autologous cell therapy. These programs potentially paved the way for next generation focus on genome regulation and allergenic CAR Treg cell therapy, where we have a robust preclinical pipeline in neurological and autoimmune diseases respectively. We're delighted with the positive momentum and look forward to updating you in the near term about several potential catalysts including presentation at ASH of four patients sickle cell disease Phase 1/2 data, presentation at ASH of two-year Phase 1/2 hemophilia data. And additionally, we'll provide a timing update for the Phase 3 trial once a proposed protocol amendment and response to the hold is shared with health authorities, dosing of the six patient and updated Fabry Phase 1/2 data presentations throughout 2022, including at a medical meeting, dosing of the first two patients in the STEADFAST Phase 1/2 study by the middle of 2022 and completion of our in-house cell therapy manufacturing facility in our Valbonne, France location following the completion of our in-house manufacturing facility in our Brisbane, California headquarters this past quarter. So we'll now turn over to the operator to open the line for questions.

Thank you, speakers. Participants, we will now begin the question-and-answer session. [Operator Instructions] Speakers, first question is from the line of Aspen Mori of Bank of America. Your line is now open.

Hey guys. Thanks for the question. So on Fabry, I think you previously, hadn't expected to share some enzyme replacement therapy withdrawal data in this year end release. It's good to see that the timeframe seems to maybe a bit faster than expected. But with that in mind, I guess, is there any patterns you're seeing in the timeframe it takes from getting from the dose of ST-920 to removal of that therapy? And it also appears that maybe the patient four kind of got to that milestone a little quicker than patient one who had a longer follow up. Just wanted to see if there's anything you're seeing there to explain that? Thank you.

So thank you for your question. I think what I'm hearing you're asking about is about ERT withdrawal. So we thought it was important to see to truly understand the effect duration. And we've been very pleased that over the course of a year and the longest treated patients, there's been a consistency of effect. And we then have discussions with the investigators and at the appropriate point for them and for their patient, they will withdraw treatment. And the first patient was only withdrawn very recently. And the second one is planned to be withdrawn this year, and so we will share that data on appropriate time.

Okay, thanks. And then I have one more on the – on Fabry. Are there any trends you're seeing among patients one and four that signal maybe what's driving a better alpha-Gal A response than you're seeing with patients two and three? I think two and three might have had a lower baseline Gb3, but if there's anything you can point to that would help out there?

Well, so there's only four patients. So it's very difficult to say anything specific. It is notable though the patients one and four are on ERT and patients two and three are not. And it may be that there is some additional effect from the ERT that is leading to that effect. But I think that is only speculation and we need to dose more patients to understand it.

Okay. Thanks, Sandy. I appreciate it.

Next question is from Yanan Zhu of Wells Fargo. Your line is now open.

Hi, thanks for taking my questions. I have a question on Fabry and maybe also additional questions on that other updates. But on Fabry, could you – Sandy comment on the dose response here and also I think for patient two, there was increase in enzyme levels above normal, but the substrate levels seems to be flat. So could you shed some light on that finding? Thanks.

So it's a good question. And I think this has been something that's been consistently seen across all of the research into Fabry disease. If the substrate levels are low, they don't change in the treatment period. But Bettina, your thoughts on this on the dose response that we've seen?

Thank you, Sandy. So as Sandy mentioned, we have now dosed two patients in cohort one and two patients in cohort two. This is still a small sample size. This needs to be emphasized at this point in time, but regarding the levels of lyso-Gb3, for sure, in three of the four patients, those lyso-Gb3 levels started off low. And as Sandy mentioned across programs, it has been seen that these remain stable, if they are low to start with – if you look at patients three, this patient's lyso-Gb3 levels start off high. And the levels of lyso-Gb3 were reduced by about 40% within 10 weeks after dosing. And this reduction was maintained through 32 weeks. So at this point in time with such a small sample size, it is really difficult to talk about those relationships. I would say that throughout 2022, we anticipate to share more data and that data will also be shared out a medical meeting, so there will be more granularity and data to come.

But I want you to take away is how excited we are by this because all four patients are above the normal physiological level. All four patients have shown consistency of response in the time that they've been served. Three of the four patients are already reporting patient effects are very encouraging about the effect of the drug. And we are already into the next higher cohort. And as Bettina says, we'll talk about this next year.

Great, thanks. And on the clinical hold for the hemophilia A, collaborated hemophilia A program, I was wondering how high is the Factor VIII level? I thought we had seen like 200% from other studies. So could you shed some light on the rationale for the – for that clinical hold? And lastly, a question on BIVV003, a very quick one that is at ASH, would we see VOC data for the treated patients? Thank you.

So I'm going to pass the question on hemophilia to Rob. Rob, can you talk to this?

Yes, we have seen elevations of Factor VIII greater than 150% in some patients. This is an ongoing Phase 3 trial, so we're not getting very specific with the data around this. There were no venous thromboembolic events associated with these elevated levels in the decision to voluntarily pause the trial was out of an abundance precaution. And as anticipated, the FDA followed through with a clinical hold that was we were notified of that late yesterday. It's our plan to with Pfizer to submit a protocol amendment and have the discussion with the agency and resume the trial when it is appropriate to do so.

And regarding sickle cell disease, we have – we'll show the full data set at ASH in December.

Great. Thanks for that updates.

Thank you.

Next question is from Luca Issi of RBC Capital. Your line is now open.

Oh, great. Thanks so much for taking my question. Congrats on all the progress. May be on Fabry disease exciting early proof-of-concept. I wondering if you can comment on how you're thinking about the Phase 3 study design? On hemophilia A, maybe if you can provide any additional color on the protocol amendment that you are thinking about to minimize the risk going forward? And then maybe on beta thal, can you just expand a little bit under rationale behind a decision to terminate a program? Thanks so much.

Goodness. So it's so exciting to be talking about Phase 3 design because we are very pleased with the results. But we need to see the results of the third cohort to really be able to understand which dose we're taking forward and how we designed the study. But I can reassure you that planning and the full energy behind the Phase 3 has already started on these programs. Let me then pass the hemophilia question to Rob and the beta thalassemia one to Mark.

Yes. With regard to the protocol amendment, we're not disclosing any of the specifics of the protocol amendment at this time. But the protocol amendment is being considered and will be submitted promptly and in discussion with the agency in response to the clinical…

And the current plan is to find the best way to guide management of any patient that has a higher level.

Yes, there'll be monitoring and management of the patients with levels of Factor VIII that are greater than 150%.

But we feel it important to restate every time that conversation comes up, no patient has come to harm. There'd be no adverse events related to this. And this is an abundance of caution. And I think a correct abundance of caution because this is a gene therapy that we need to take very seriously and do the best for the patients. Mark?

Yes. So in terms of the beta thal decision, it was really a business decision that we took alongside our partners at Sanofi just due to the timing and relative to where the competitive set lies in terms of their development. We felt that it is important to really focus our effort and our resources solely on sickle cell disease.

And drive forward together.

Got it. Thanks so much guys.

Next question is from Maury Raycroft of Jefferies. Your line is now open.

Hi, everyone. Good morning and congrats on the update today. For Fabry, just wondering if you can talk more about the alpha-Gal data being two to 15 fold higher than normal, seems higher than competitor data at month 12 that showed about five to six fold higher. I guess what's the best way to contextualize your data versus competitors and how could this translate to kidney substrate reduction?

Thank you, Maury. Bettina, do you want to talk about Fabry?

Sure. Thank you, Sandy. So in terms of the alpha-Gal data, we're obviously very excited to see the super physiologic alpha-Gal expression that we are seeing with all four patients. I think at this point, it is early to compare and probably not the right place to do comparisons across programs. We look forward to sharing more granularity on this data at an upcoming meeting in 2022. So that also goes to any additional data related to kidney substrates.

You can imagine though, that having seen efficacy at the two initial cohorts and moving into third higher cohort and it gives us enormous energy that this is going to be a medicine that will be useful for patients with Fabry. It really is compelling data early as it is, we find it compelling data.

And I would add that on priority, we had targeted super physiologic expressions of alpha gal A and plasma to drive clearance from tissues. So this is a desired affect of what we're seeing.

Got it. That's all helpful. And maybe just one follow-up, if you can compare and contrast the Fabry observations and gene expression and dose with your hemophilia gene therapy program. Maybe if you can talk more about that.

That's a good question. We are fortunate that we've used AAV6 now in several programs and we understand the safety of it. And across all of the programs, we've had very few adverse events. In addition, if you look at the point at which there's an inflection of efficacy, it's about the one to three E13 in hemophilia, and it's even earlier than that in the Fabry disease program. Other than that, we're very pleased with the safety and efficacy we've now seen in our two gene therapy program.

Got it. Okay. Thanks for taking my questions. Congrats again.

Next question is from Nicole Germino of Truist Securities. Your line is now open.

Good morning, thanks for taking my questions and congrats on the progress. So I dialed in a little bit late and I might have missed some of the opening remarks. So I apologize if my questions were already addressed. But for Fabry, can you talk about how the primary symptoms have improved over time from baseline and any color on cardiac function? And for Heme A, how long from infusion did these excursions happen and how often are Fabry levels being assessed going forward to monitor?

So your line is a little unclear. So let me see that – read back to see, I understand your question is about the patient symptoms in Fabry, and it's about how we manage the patients in hemophilia. Is that correct?

Yes. And how long for hemophilia, how long from the infusion did these excursions happen?

So Bettina, can you say what we know about the patient reported symptoms in Fabry please?

Yes, of course. So, as a reminder, again, I'd like to emphasize this is early data that we're sharing, early preliminary data, the patients, one, two, three of the four patients had an hidrosis reported at baseline. And some of these patients, these three patients have reported improvement in sweating or post duration which is an favorable outcome for patients in the time period over the course of the study that we have seen so far. One of the patients also have had seen stabilization of cardiac structure on serial assessments on imaging. So these are preliminary reports that we are gathering. And as I mentioned before, we will be sharing more information over the course of next year of some of these details.

I'd like to add that if you look at the totality of the data, including the patients’ observations that were relayed to the investigators, the alpha gal expression, the adverse events, that all of the data are all pointing in any favorable direction. So we would like you to look at data in its totality, not just each individual component.

Great. And then for Heme A, how long from the infusion did the excursions happen?

This is an ongoing Phase 3 trial, so we aren't disclosing the specifics around the data. We want to keep that Phase 3 trial protected because it's a potential registration trial.

Great, thanks.

Next question is from Gena Wang of Barclays. Your line is now open.

This is Tom for Gena. Thanks for taking the question. So for the Fabry, just one question with dosing and the alpha gal enzyme level, do you plan to dose higher depending on the data readout and what is your automated goal of that level in the serum is current super physiological level enough? And how about the alpha gal enzyme change after the patient who withdrawed from the ERT and for the Heme A?

Great questions. Can we do Fabry first? So we make sure we cover all your questions. We've never set it must be this for alpha gal because this is the first time that people have really done gene therapy in Fabry disease. And so there isn't a definitive level. We've always thought it had to be better than normal physiological levels. And we're pleased to eat the patients both on ERT and off EET are at that level. And now what we are doing is withdrawing the ERT and seeing where the levels provided by the gene therapy and the liver level out. And until we do that experiment, we really won't understand this fully. We are also dosing at 3E13, which is three times higher than the current dose. And once we see that data in its totality, we'll be able to decide which dose to take forward into Phase 3 but we felt the first two cohorts were so compelling as Rob says, with the alpha gal, with the patient safety, with the patient related outcomes that came spontaneously from patients talking to the investigator about things that had been, that are important to them, like ability to exercise, because they can now swear that we felt that this data was exciting and compelling and wanted to share it with the broader community.

Okay, great. That's very helpful. And maybe just quick follow up on the Fabry that you comment that you will share additional data, including the clinic function data in the 2022 in medical meeting. And will that be include Gb3 kidney inclusion or it will be EGFR, the filtration function measurement. Can you set – help us to set an expectation for that?

It's unlikely that we'll be sharing renal biopsy data in 2022, there's the patient would undergo an initial biopsy and then some months later a second one. So that data is unlikely to be available in 2022.

Okay. Thanks for that. And for the Heme A so we know that will be, there will be protocol amendment. And other than do you expect any additional steps that require in order to remove the clinical hold or the implementation of the oral anticoagulant will be the only one that would be required?

I have enormous confidence in our colleagues with Pfizer that put together an amendment that puts patients first and makes sure that the patients always remain safe. And then they will discuss that and present it to the agency. And hopefully we'll be able to move forward with this trial. As Pfizer have said, over 50% of the patients have been enrolled now and they've had an a pre-study to collect the patients, to have them ready to go into the trial. So we think this will move forward and are sure that Pfizer's doing the right thing.

Okay. Thanks for that.

Next question is from Ritu Baral of Cowen. Your line is now open.

Hi guys. Thanks for taking the question. As part of this Phase 1/2, what other clinical I guess, a clinical quality of life or patient reported symptomatology, are you capturing Sandy? You mentioned improvement in sweating. Are there other things that are being proactively asked clinical symptomatology wise? And then can you talk at all about sort of the curve of expression that you're seeing like for patient one that 15 fold at week 52? Can you confirm that that's like the top expression that you've seen and for patient four that you're sort of continuing on your way up and anything you can say about the curve?

Okay. So we measure a whole slew of things, including formal patient related outcomes. We want to be very clear. This was spontaneous – patients spontaneously talking to their investigator to tell them of their – of the changes that they’ve known. And the investigator will felt compelled to tell us because it was important. We will measure this going on in the Phase 3. And because it’s not just about the enzyme what’s important is what’s important to the patient and it’s things like the neuropathic like pain that they have. It’s about the sweating, it’s about the quality of their life and their energy and so we want to capture all these things. Second question, I think that you’re asking is about duration that’s very pleasing to us because this is a solution we want for as long as possible for those patients. And in all of the patients after once it gets to its plate level, it has remained at that level throughout the duration of the study and the – we will continue to follow these patients and report the – hopefully the continued duration of the fact.

Got it. And just given the change in the – I guess the regulatory landscape in Fabry over the last 12 months or so. Are there any plans to potentially add a biopsy to this study? Or are you – is that going to be reserved for the next study kidney biopsy I mean?

We have plans for biopsy in this study. It’s just that the results will not be available within the 2022 phase. We’ve always said that we would not do the biopsy in the initial patients until we saw that the medicine was effective and now we see the medicines effective biopsies will be part of the routine of the study.

Got it. Okay. So maybe not these biopsy from these patients, but maybe the fifth and six patient with the highest dose. Is that the plan?

So the first four patients did not have renal biopsy and future patients will.

Okay.

As part of the study protocol.

Got it. Thanks for taking the questions.

Our pleasure.

Next question is from Ben Burnett of Stifel. Your line is now open.

Hey, thank you very much. I will echo my congratulations on the Fabry disease data. I did want to ask a couple questions around this. The first one, I would also agree with some of the others on the call. It seems like the enzyme activity is quite good at least relative to competitors. But I guess just curious that the impact on lyso-Gb3, just wasn’t more profound specific on patients one, two and four. I guess how – what is your interpretation of those data and how representative is lyso-Gb3 in the plasma to what’s happening inside of cells?

Good question. Until we biopsy, we won’t have that direct correlation. I’ll say again, in all of the Fabry trials from each of our competitors and us patients who have low lyso-Gb3 don’t go lower. If it’s already very low, it’s hard to make it go lower. And that’s across all of the trials. And yet, even in the trials that have done Gb3 even in the AVROBIO trial, for example, who showed a reduction in Gb3 in the kidney. They also showed that effect that it had to be high lyso-Gb3 to show a reduction in the plasma. It’s a very different system that we’re producing here. We think this is what patients want. They want a one-time injection that is safe, that is effective at producing alpha-Gal and is effective at producing an over a long period of time. And that they notice a benefit and we are already having indications that that’s what’s seen. Now we need to go to the next hire dose and hopefully show even more benefit and then pull all that data together and decide on the full design of this study for Phase 3 and get this medicine to patients as soon as possible. We are very pleased with the safety, the efficacy, the consistency, and the patient benefit we’ve seen so far.

Understood. Okay. That’s helpful. And if I could just ask one sort of clarifying question on patient four alpha-Gal activity at week 14, you show an assessment that looks, I think really good, but was this assessment made after they were weaned off of enzyme replacement therapy? Or was that prior to that?

Bettina, can you just clarity to that?

Absolutely. So patient number four has only been withdrawn from ERT therapy very recently. And after the cutoff data for what you’re seeing on these slides that we have posted on our corporate website. So the data you’re seeing is with the patients still on ERT. And just to clarify, all the data points are at trust ERT level. So dosing was is prior to the ERT infusion. So the ERT withdrawal will have been after this data cut.

Okay, okay.

And it’s part of the reason that this therapy is I think offers a better solution than ERT, is ERT has a very rapid Cmax and then it declines quickly, but we wanted to be particularly careful. And therefore we measured the trough level, usually about day 14 after the ERT at the very last point before the patient had their next dose of ERT to make sure there was no residual enzyme in the plasma. And that’s something I think we all – in all the different studies from all the different companies need to be careful about is making sure that the trough is the trough.

Understood. That makes sense. Okay. All right. Thank you very much for the color.

Thank you,

Speakers we have time for one more question from Andreas Argyrides of Wedbush Securities. Your line is now open.

Hi, good morning, and thank you for taking our questions. Let me also reiterate our congrats on this early encouraging data. Yes. So for Fabry, just a quick one on the preexisting antibodies, your thoughts around any potential impact that may have. And then on the hemophilia A, does the protocol amendment restart the time for the ABR data? Thank you.

So let me answer the second one then pass the antibodies to Bettina. Why this had to be treated seriously was these are patients in gene therapy. So when they get the meds and it stays in their body, even if the trial is paused. And so we and Pfizer will continue to collect data from the patients, even though the recruitment into is paused. There’s still information about prolongation of effect and safety of the medicine being collected by Pfizer. So it’s unusual compare to a pause trial where the patient stops taking the medicine. The medicine is still there and continuing to have benefit for the patient we hope. Bettina, the antibodies?

Yes. For the antibodies, so I think what is important to emphasize is, this is early data on four patients. And it is early to make inferences as to whether antibodies and to what degree antibodies are having an effect on these patients. We need to bear in mind that two of these patients are on ERT to are not. There is a lot of variability in the data at this point in time. So we look forward to seeing more data coming out from our next cohort, Cohort 3, and being able to assess that impact in a better manner.

And we – but we haven’t seen anything, any correlation optimal.

At this point in time, that would be difficult to say.

Sure. Okay. Understandable. Thank you for taking that our questions and again congrats on encouraging data. Thanks.

Thank you, participants. I’ll now turn a call back over to Aron Feingold for closing remarks.

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

That concludes today’s conference call. Thank you all for joining. You may now disconnect.