Good day and thank you for standing by. Welcome to the Sangamo Therapeutics Fourth Quarter and Full Year 2021 Conference Call. At this time all participants are in listen only mode. After the speaker’s presentation there will be a question and answer session. [Operator Instructions] I’d now like to hand the conference over to your host today.

Aron Feingold, Head of Corporate Communications, please go ahead..

Good afternoon and thank you for joining us today.

With me this afternoon 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, 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 candidate, the anticipated plans and timelines 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 initial 2022 financial guidance and other statements that are not historical facts. Actual results may differ materially from what we discussed today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC.

Specifically, 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’ll 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..

Thanks Aron and good afternoon to everybody on the call. I’d like to start by saying that 2021 was a significant year for Sangamo as we continue to advance the development of genomic medicines for patients across multiple therapeutic areas using our innovative technologies.

We’re very pleased with our progress despite the challenges as the second year of the pandemic. We’re advancing potentially transformative genomic medicines in the clinic, and strategically using our R&D capabilities to pursue indications of unmet need.

These efforts are supported by our manufacturing infrastructure, including in-house, AV and cell therapy facilities. Our collaboration partners also help us drive towards our mission to deliver on the promise of genomic medicine. And we believe that this progress positions us as well to generate long-term value for our shareholders.

In 2021, we executed upon our strategy with several important achievements. First, we and our partners advanced our three lead programs for presenting compelling clinical data. Starting with our wholly owned Phase 1/2 Fabry disease program, we presented updated data at the World symposium earlier this month.

We’re encouraged by the safety and efficacy data we have seen to-date. And most importantly, the patients in the study report that they’re feeling better. Investigators observing improvement, some of them was challenging symptoms, including ability to sweat in the first three treated patients.

With the recent changes in the Fabry competitive landscape, we believe we’re in a leading position. In the second half of this year, we plan to present additional updated Phase 1/2 date. We’re actively planning for a Phase 3 study, including discussions with health authorities, patient advocacy groups, and investigators.

Were also delighted by the emerging Phase 1/2 sickle cell disease data presented at ASH in December, showing no treatment of adverse events in the four treated patients improvement across several biomarkers, and most importantly, clinically significant reduction and painful sickling crisis.

We anticipate that the next four patients treated in the study will be dosed with a product candidate manufactured using improved methods that have been shown in the internal experiments to increase long-term progenitor cells. We expect to complete dosing of these patients in the third quarter of this year.

Transition planning of the program from Sanofi to Sangamo is going well, and we are energized to have this asset back in our hands soon as we assess the best way to move the program forward for patients be that on our own, or with a potential partner.

Finally, we’re encouraged by the follow up data presented at ASH last year from our Haemophilia A program partnered with Pfizer. Updated Phase 1/2 results show sustained bleeding control in the highest dose cohort to two years following gene therapy.

Regarding the Phase 3 study, Pfizer has announced that it hopes to obtain agreements with the health authorities to resume their AFFINE trial in the first half of 2022. The trial was previously paused when some of the patients experienced Factor VIII activity greater than 150% following treatment.

Pfizer is currently in the process of submitting a protocol amendment to health authorities in the countries where this trial has been conducted, and preparing responses to the FDA clinical hold. Over 50% of the patients have been enrolled in the Phase 3 of AFFINE trial.

Second, we’re progressing our preclinical candidates based on our second generation technologies, CAR Treg for autoimmune disease and Zinc Finger Transcription factors for neurological disorders.

We have enrolled and expect to dose soon the first patient in our elite CAR Treg program where we are evaluating TX200 for the prevention of immune mediated rejection in HLA-A2 mismatch kidney transplant from a living donor.

We believe that this will be the first patient ever to be dosed with a CAR Treg therapy and that we are in a leading position with several companies following us into this very promising area.

We believe that our expertise across multiple technology platforms robust cell therapy infrastructure, supported by our manufacturing facilities and genomic engineering capabilities, and internal strategic and operational synergies comprise a differentiated CAR Treg platform for which we can potentially offer patients advanced genomic medicines.

In addition to a proof of concept study of TX200, we are progressing our preclinical allogeneic renal transplant rejection study, as well as inflammatory bowel disorder and multiple sclerosis programs, including presenting in the first preclinical data from our allogeneic IL 23R CAR Treg candidate in IBD last year.

And finally, with regard to our zinc finger protein transcription factor technology in treating CNS disorders, in addition to our partnered programs with Biogen, Novartis, Takeda and Pfizer, we’re advancing multiple internal programs.

Third, we continue to hone our differentiated genome engineering platform, including improving the specificity, precision, and efficiency of our core zinc finger proteins. We’re also progressing our capabilities from nucleases to repressors, activators, and even bass editors and are excited about our progress.

We see Sangamo’s capabilities as representing a one stop shop for a range of genomic engineering capabilities. They’re designed to be applied therapeutically.

Fourth, we continue to work diligently with our collaborators supporting the advancement of our partnered programs in the clinic, while driving research efforts for preclinical programs for which we receive reimbursement from our partners. These partnerships have been a key component of our development strategy and continue to drive value for cycle.

We believe that the buy in from pharma validates a mechanistic approach across a range of advanced modalities, and enables us to benefit substantially from a partner’s domain expertise to develop high quality therapeutics for patients.

The capital provided by our partnerships helps advance our internal pipeline of assets, while providing our partnered programs with the resources needed to advance the development of these potentially transformative therapies more quickly. Fifth, we completed and brought online our cell therapy manufacturing facilities in Brisbane and Valbonne.

And now have operational AV and cell therapy facilities in-house. We believe these facilities provide many strategic advantages, including flexibility and control, capacity can support our R&D needs, process expertise, geographic diversification, and that supports supply chain resilience, and a deep intellectual property portfolio.

Six, we believe that we have a strong financial position to take us through overseeing incoming catalysts. Our diverse and accomplished leadership team and our talented employees are passionate about our mission, and have enabled our multiple 2021 accomplishments setting us up for what we expect to be a strong 2022.

I am very grateful to my leadership team and all my salable colleagues for their dedication and hard work in a second challenging year of the pandemic. And with that, I’d like to turn the call over to our Head of Development, Rob Schott, who will discuss the data for our clinical programs in more detail..

Thanks, Sandy, and good afternoon to everyone on the call. We are delighted by our clinical execution in 2021. We believe the presentation last year of important proof of concept data supports late stage development for our Fabry and sickle cell program.

At the World symposium earlier this month, we presented updated preliminary results from the Phase 1/2 star clinical study evaluating isaralgagene civaparvovec or ST-920, Fabry gene therapy candidate for the treatment of Fabry disease.

As of the November 9, 2021 cutoff date, the gene therapy candidate continued to be generally well tolerated across three dose cohorts in the five treated patients with treatment related adverse events that were assessed as grade one or mild.

Elevated alpha-Gal activity has been maintained for the four patients treated in the first two dose cohorts ranging from threefold to 15-fold above mean normal at last measurement.

For the two patients on enzyme replacement therapy alpha-Gal activity measured at ERT trough was 15-fold above mean normal at week 52 of the patient in cohort one and 10 fold above mean normal at week 25 for the patients in Cohort 2 through the two ERT pseudo naive patient alpha-Gal a activity with three folds above mean normal at week 52 for the patient in Cohort 1 and four fold above mean normal at week 40 for the patients in Cohort 2.

The two patients in Cohort 1 have now begun the long-term follow up study and at the one year mark, alpha-Gal A expression remains robust. Withdrawal from ERT has been completed for one patient and is planned for the second patient on enzyme replacement therapy based on the stability of their alpha-Gal activity following treatment.

For the first patient in Cohort 2, alpha-Gal A activity has increased into the mean normal range at week 2. As Sandy noted, three of the patients that reported clinical improvement with a greater ability to sweat. This allows for greater exercise tolerance and active individuals.

The cardiac magnetic resonance imaging data suggests stabilization of important MRI parameters in two patients. This will be followed in intervals to confirm the cardiac benefits of therapy.

The one patient with a significant elevation in plasma lyso-Gb3 pretreatment showed a significant reduction from baseline of approximately 40% in this biomarker treatment with SP920 within 10 weeks after dosing, and maintained through Week 36. Patients with lower baseline levels of lyso-Gb3 maintained steady levels during the cutoff date.

The sixth patient in the study, who is the second patient in Cohort 3 was recently dosed after the cutoff date. We expect to provide updated results from the star study in the second half of 2022 and are currently planning for a Phase 3 clinical trial.

At ASH 2021, we announced updated preliminary proof of concept data from the Phase 1/2 precision one study of SAR 445136 for the treatment of sickle cell disease. As of the September 22, 2021 cutoff date, the most recently treated patients in the study has been followed for 26 weeks, and the longest treated patient had been followed for 91 weeks.

In all four treated patients there were increases in total hemoglobin, fetal hemoglobin and percent F cells. None required blood transfusions post engraftment the SAR445136 investigational drug product had on target BCL 11, a gene modification of between 61 to 78% in all four patients.

There were no adverse events related to therapy with SAR445136, one patient had a single sickle cell crisis or vaso occlusive crisis, nine months after treatment, there have been no additional serious adverse events reported. Additional data from this study are expected to be presented at a medical meeting in 2022.

And dosing the patients in this study is expected to be completed by the third quarter of 2022. We are currently collaborating with Sanofi on planning for a transfer of its responsibilities under this program, back to Sangoma this June. We look forward to keeping you apprised of future updates regarding these exciting clinical studies.

With that, I’ll turn it over to Prathyusha for a financial update. Prathyusha..

Thank you, Rob and good afternoon. Our financial results for the fourth quarter and the full year are available in the press release issued and can also be found on our website.

I want to reiterate that 2021 was a significant year for Sangamo with execution on many fronts as we continue to progress the advancement of our lead programs, our preclinical research pipeline, and our in-house manufacturing capabilities.

With approximately $465 million in cash, cash equivalents and marketable securities at the end of the year, we believe that our balance sheet remains for continued execution across our platform and programs. Turning to our initial 2022 full year guidance, we expect non-GAAP operating expenses to be between $280 million to $310 million for the year.

This range excludes estimated non-cash stock based compensation expense of approximately $40 million. We expect a significant portion of our operating expenses to be invested in continued progress of elite programs, including Fabry pre-planning activity, Phase1/2 activity for TX200 and preclinical work and CAR Treg and CNS indications.

We also expect to grow our investment in sickle cells in the second half of the year, following the [Indiscernible] I will now turn the call back to Sandy for closing remarks..

Thank you, Prathyusha. We’re excited by where we stand as a company and believe we have a bright future. We are a fully integrated genomic medicine company building momentum with our noble thoughts, clinical execution and in-house manufacturing.

In 2022, we look forward to providing expected updates on Phase 1/2 Fabry data, selection of a dose for Cohort expansion and Phase 3 planning.

Dosing of patients in the CAR Treg steadfast trial Phase 1/2 Sickle Cell Data and dosing of patients in the precision one study and the transition of the program from Sanofi to Sangamo and Pfizer’s progress for the pivotal Phase 3 Haemophilia A trial. We’ll now turn it over to the operator to open the line for questions..

[Operator Instructions] Our first question comes from Nicole Germino with Truist Securities..

Good afternoon, everyone. And thank you for taking my questions and congrats on all the progress. If I could ask a two part question. The first one is, in the backdrop of other companies experiencing clinical holes with their gene therapy programs.

Can you address the safety concerns the integration rest around your vector for Heme A and for ST-920 for Fabry.

And second, for your CAR Treg platform, how necessary is it for a kill switch for regulatory agencies? Or maybe put another way, will give you confidence that you don’t need?.

So thank you for your questions. So if I could address the first one, and then I’ll pass the second one on to Rob. So safety is really important to us. And that’s why we look on safety as the primary endpoint of all of the studies that we’ve done with our AVV6 factor.

We’ve been really pleased by the safety throughout all of the programs, the MPS programs, haemophilia A, and now with Fabry disease, and we’re gathering an increasing body of data that convinces us that this form of delivery is safe for the patients that we serve.

The choice of diseases remains important because we always have to balance benefit and risk. And we spend a long time thoughtfully gathering preclinical data sharing with the regulators, starting doses that allow us to be sure that patient safety is maximally protected. And then sharing with the community any concerns we have as the trial progresses.

I’m delighted with our progress so far. I think it’s unfortunate and others have run into difficulties because it does close the whole field. I’d say advantage of us having effect to that we’ve worked with and have gathered a lot of safety..

Yes. I’d like some clarification to call on the kill switch and you’re suggesting that we’ve programmed that into the cell therapy so that we can turn off the Tregs. Is that the --.

Yes.

A couple of your competitors have, a kill switch, is it necessary for regulatory agencies, have regulatory agencies had any input on this? And if not, like, is it? Do you need a kill switch or will give you confidence you don’t need one?.

Yes, we’ve not been asked to in here, kill switch. Again, these are T regulatory cells that were engineering through these programs. So they are responsible for inhibiting the immunologic response and rejection in the case of renal transplant. So it’s a different proposition that engineering other types of T cells, killer T cells are CDA T cells.

But I’d actually like to have Jason to comment on that, too.

Jason, can you help us?.

Yes, thanks, Sandy and Rob. Yes, I think what I can say is that we’re very confident about the approach that we’re using in the TX 200 program. We’ve evaluated the safety and the efficacy of the cells in a variety of preclinical models.

And we’ve been very happy with what we’ve seen, we’ve obviously consulted with our own internal experts, clinical regulatory safety, and we’ve had conversations with the regulators and are moving forward. And we’re excited to be dosing our first patient in this quarter.

And other companies take different approaches, but we’re confident that our approach is one that is going to offer a benefit for patients. And we’ll be keeping a close eye on patients as they’re treated. Obviously, this is a Phase 1 study where safety is paramount and that’s what our focus is on..

Thank you, Jason..

Our next question comes from Yanan Zhu of Wells Fargo..

Thanks for taking my questions. First on Fabry program, so you mentioned you will have additional data in the second half of the year that you’re wondering what might be the follow up? And presumably this is going to include all six patients.

So the question is the length of the follow up and informative endpoints? I think we can assume ERT is the important endpoint, enzyme level substrate.

But would there be any additional clinical endpoints that’s also going to be studied? To be reported at that stage?.

Thank you for your question. So this is about the longer term return on Fabry and what we’ll be able to show, Prathyusha you can find this chart very closely..

Yes, and thank you so much for the question. So later on this year, we will have accumulated more data, especially from the earlier dose patients.

You may know the parents studies, these patients have been enrolled into the one year study in patients that have been treated at the beginning, have some of these patients have now rolled over to the long-term follow up study, which is an additional four years of follow up in total.

And we will be able to prevent data on accumulation of the Alpha Gal A expression over time, as well as other biomarkers like GB3, and you point out your T withdrawal data.

And in terms of clinical endpoints, we will be collecting one sweep those naive patients moving forward, we will be collecting kidney biopsy data this will not be available this year. At this later update, we can expect that type of clinical data to be presented. Next year, we will also be presenting an update on patient reported outcome.

And so really, we move along, we are also intending to those more patients and we have patients currently in screening and in baseline. So patients are going to, we anticipate to be dosed. And exactly and some that will be a nice profile that we will be collecting from this wealth of data as well..

We like from the data we’ve seen so far is up until the one year mark that we have complete data from, there’s been no sense of decline in four patients that have been treated for the longest that the Alpha gal is remains elevated, the lyso Gb3 remains flat, the patient’s remaining is still getting a claim of benefits, talk about symptoms like sweating, talk about, their investigators talk about stabilization, and MRI.

And those are all really encouraging data that it’s only through time that we’ll be able to understand. However, I want to be absolutely clear, we are full on in our planning for the Phase 3 study and look forward to initiating that as the data from the current study matures..

Right. Yes. Thank you. And looking forward to hearing about the Phase 3 design. So I think maybe too early to ask that question. So I might, if I may, I’m curious about what you mentioned about ace editing programs that you’re working on. Obviously, this is going to be based on zinc fingers.

So my question is, does your based editor retain the nucleus part of the big thinker nucleus? Or does it forego that nucleus part of the reason I’m asking is because I think in the base editors, actually in this case capability i.e., the ability to cut one strand of the double stranded DNA is actually very useful in terms of improving the editing efficiency, because it prevents the degradation of the edited strand.

So under that light, so I’m interested in whether your architecture for your base editor basically. Thanks.

Very interesting question. So we’ve been working on this for some time and I’ll get Jason to comment in a minute.

What gives us great pleasure is that the same thing, our platform allows a range of technologies to be added to the DNA localizing zinc finger and allows us to choose when double stranded breaks and nuclease are important, or whether things like repression enhancement, or these editors are the right things for the right patient.

Compared to crisper, there’s a company for each of these.

But Jason, can you comment on the specific question, please?.

Sure, thank you, Sandy. This is a base editor that will not create double stranded breaks to change a base in the genome. And we’re really excited about the advancements that we made, and we look forward to sharing them very soon, at the appropriate scientific conference.

I don’t think I’m going to go into the details of the architecture of the base editor that we’ve designed, but it’s a novel approach. And we’re very excited about discussing it and deploying it therapeutically..

Great. Thanks for the color..

The reason we particularly like it is it uses a zinc finger architecture we’ve had years of experience with until understanding about how to tune and how to increase the specificity.

It benefits from the small size of zinc fingers, and which are almost a 10th the size of some of the crisper architectures and therefore allow it to be packaged in AV in a way that the standard base editor won’t. And it allows us choice, and that’s what we like, and that’s what our partners like..

Got it? Yes. Thanks. Thanks for highlighting that advantage. Yes, that’s a question in my mind, as well. Thank you very much for all the color..

Our next question comes from Maury Raycroft with Jefferies..

Hi, thank you for taking my question, [Indiscernible]. So actually, I have two questions. The first one is can you talk more about where you are at the designing a Fabry’s Phase 3? And what are the gating factors to get all this study’s been started. That’s my first question.

Second one is, what else can you talk about the first patients enrolled in the CAR Treg program? And can also say if this patient has already been transplanted and are you currently processing the CAR Treg? That’s my question..

So let me take the easier one, which is up anymore. Can you just talk about where we are with text in general, please. So we haven’t shared anything about the Phase 3 study, but as I’m sure you know, planning for a Phase 3 takes a long time.

And therefore we’ve been looking at the design of this and talking to experts for at least six months, and are pleased with the progress we’re making. And we’ll share more broadly at the right time.

Mark can you talk about the risks because we’re very excited about that?.

Yes, so we’re about to just the first patient with our TX 200 candidate. And so we’re very excited about that. And as we’ve talked about, we’ll be expecting to dose two patients by the end of the second half 2022.

We’re delighted to take this forward, because it’ll be the first opportunity for us to really establish the biologic effect of these agents, and really understand what’s going on. And this is critical because our goal is that TX 200 establishes the foundation for a portfolio of CAR Tregs for major auto immune indications.

And so this will inform us, using the autologous. In the meantime, we’re advancing allogeneic approaches. And as we’ve disclosed, we’ve got preclinical candidates against multiple sclerosis, as well as IL 23R for inflammatory bowel disease.

And so we’ll be applying the learning that we have coming out of this trial as we advance the platform, but also those particular candidates..

Great. Thank you. Thank you very much..

Our next question comes from Luca Issi with RBC Capital..

Great, thanks so much for taking question. Congrats on the progress.

Two quick one, maybe the first on Fabry, I will not ask you the design of the Phase 3, but maybe at high level, can you just talk about what gives you confidence and you can start a Phase 3 here without actually having seen the kidney biopsy data quite yet? And then maybe second on sickle cell disease, can you just provide any additional color on the new manufacturing process here.

What are some of the key parameters that you’re optimizing here to give you confidence that the new manufacturing process will drive better outcome for patients? Thanks so much..

So let me see how I can split these. Rob, can you talk about sickle, please? And the other question, I think you said was in the absence of inflation, we answered this question correctly. And in the absence of kidney biopsy data, which we expect to see in 23, how will we decide on the go decision and the design of the Phase 3.

As I said, we’ve been designing this and talking with regulators for some time.

And we believe that the data, perhaps from Afro Bio, one of our competitors, where they showed very small changes in alpha Gal we get changes in the renal biopsy data for ICG, V3, that in itself gives us confidence that the Alpha gal we are seeing should benefit the tissues when we get to that stage. So we have to plan in advance.

And we have to look at the different doses and the dose response curve, and decide which one we take forward as we accrue data..

And with respect to the sickle cell program in manufacturing, we have made some process changes, we haven’t talked specifically about this process changes but in, in internal experiments, we’ve shown it increases the number of progenitor cells. So we’re optimistic that this will carry through into the clinic with better yield..

And we’re being very transparent. And I hope realistic to say that we believe these will results of clinical benefit. But until we do the clinical experiment, we can’t have a direct correlation. So that’s why we too are very interested in seeing the data from these next three or four patients that will be dosed over the coming months.

And I want to say thank you to our friends at Sanofi, who are continuing to drive forward the study during the transition period..

Got it? Thanks so much..

Our next question comes from Ben Burnett with Stifel..

Hi, this is Kelly Brees on for Ben, thanks for taking our questions. I just had one, quick one about Fabry. So regarding the Fabry program, can you talk at all about the life of GB3 biomarkers specifically under what situations would you expect the biomarkers to move with ST-920 treatment? And then our second one is about hemophilia.

And I was just wondering if Pfizer has already received feedback from the FDA and the necessary steps to remove the clinical holds? Or if this is something they have yet to do. Thank you..

So Prathyusha, can you do Fabry and Rob for hemophilia?.

Yes, thank you for the questions. So like for GB3, you will have seen we presented data on at the world’s symposium just a couple of weeks ago in San Diego. And different patients are exhibiting different baseline level to start off with lyso GB3.

And so the movements that we can expect are going to differ based on this, I’d like to point to patient number three, who is the patient, first patients in cohort 2, whose lyso GB3 started higher than the other patients and for whom we’ve had significant more than 40% reduction.

And that within the first 10 weeks post infusion, and that reduction has been maintained over time until the latest follow up. And so, we look forward to is seeing the next patient going to be dosing, seeing how they’re likely to be three phase over time, depending on their baseline..

And this phenomenon Prathyusha has been seen in other adult programs, it’s got to be hard to do..

It’s important to point that out, thank you Sandy, because we have seen the same in other programs that the lyso GB3 really does need to be at significantly high levels for us to be able to impact it with a gene therapy approach and that has been seen across other programs.

And so we’re confident that we’re seeing data that is going to be encouraging as we also look at our next patient’s dose at the higher dose..

And Rob hemophilia..

Hemophilia. First I’d like to acknowledge the terrific partnership with Pfizer on this program and remind everyone that the trough was more than 50% at the time of this class. Pfizer has guided us in markets that trial will resume or planning to resume in the first half of 2022.

So without getting into the specifics where we are with responding to regulatory authorities, I can point toward that guidance of resumption trial, in the first half of this year..

It’s going pretty well, and they’re putting all their efforts..

They are aggressively and enthusiastically pursuing this trial..

Our next question comes from Aspen Mori with Bank of America..

Hi, guys, thanks for the question. Maybe you can just talk through your updated thinking as you transition that six, is that over to you guys. Maybe stuck the update thinking on how you see that progressing in terms of ticking it alone or maybe partnering it out.

And if the priority is partnering, if there’s any preference for someone with more of an US presence as that was kind of Sanofi niche in your prior partner? And then the second question, some of your peers have implied that for the gene therapy space, FDA may be stricter on therapies or indications where there’s already approved therapies available.

Do you think that’s a fair assessment? Or has that at all been, have you kind of seen that dynamic play out within your interactions with FDA? Thank you..

I’m going to ask Mark to talk about the strategy around sickle. And then I’ll touch on the general comment..

I mean, obviously, we heard December 30, they had made that strategic decision to transition sickle cell back to us. As Sandy mentioned, the team has been working very hard on the transition, we’re very pleased with the engagement we have with Sanofi, as we progress to the transition plan, which will culminate around June 28 of this year.

Our highest priority right now is to ensure that we can complete the Phase 1/2 precision trial, as Rob just mentioned, utilizing that new manufacturing process, which we hope will come through and demonstrate even better results in those four patients.

Totality of that data will inform kind of the way we want to proceed forward, in the meantime the teams have engaged the authorities, both in terms of feedback on manufacturing, as well as preliminary discussions around the approach to Phase 3. So at the appropriate time, we’ll provide an update for that.

In terms of the geographies and partnerships, we’re not going to comment on that now. It’s too early to provide a perspective on that. But I would remind you right that in the United States through about 100,000 sickle cell patients, of which 30,000 of those patients are severe. Outside of the US, there’s about 150,000 patients.

This is a devastating disease that affects a particular population. And our commitment is to do whatever we can to make sure that patients get access to this medicine, if it’s a differentiated medicine. And we’ll know more as we get the clinical data. And our commitment is to ensure that we take it forward if it’s the data subjects issue..

And if I could talk to the more general one about the agency. We have a great relationship with agency and I have an enormous respect for Peter and the FDA. Because I think one has to understand the exponential growth in this field that they have to deal with and to train people and to stay ahead of the emerging data and understanding.

I think there is a bit of a reality check that we’re watching now, which is more medicines are in the clinic, more new factors are being tested, and some of them will be found to have challenges and that’s inevitable in any new field, which takes me back to what I said to one of the earlier questions about our effect or having had years of testing in many indications of the team at Sangoma having too many IND understanding the preclinical toxicology data necessary to ensure safety and about the inherent unemployed in the same model, it’s everything is about the patient and that the patient safety first.

And would be the first to have that conversation with the agency, if we are ever concerned about what we’re seeing. But at the moment, we haven’t felt any difference in the agency’s approach, and are glad to have them as partners in the development of our medicines..

Thanks, Sandy..

Our next question comes from Ritu Baral with Cowen..

Good afternoon, guys. Thanks for taking the question. I had a question on the precision one. Well, the sickle cell program in general, I think at a high level, I’d love to know the metrics by which you’ll gauge sort of where the program will fit in a landscape that’s getting more and more crowded.

And to drill down on that, I guess what we’re looking for is Hbf levels, but also percent F cells I guess, which one do you think will be more important or more important to tell on the ultimate clinical benefit? And especially since you’re reaching such high levels of percent F, do you need to do you need to show that sort of 90s level of percent F cells in a certain proportion of treated patients for you to say that this is going to be the preferred therapeutic..

So, I’m going to ask Rob to comment on the technical more strategic that what would remind you, we’re in the clinic with clinical data, there are many, the competitive landscape is largely of new comers from other editing modalities, getting into the pipeline and talking a bit.

But Rob, can you talk about what you’re used to or successful?.

What’s most important to the patient is the frequency of which they have been to occlusive crisis. That is the most important parameter is releases of painful, expensive sickle cell crisis.

And what we have seen in the four patients that we’ve reported is an enormous effect size, we’ve had a single VOC, whereas prior to treatment, they were having very frequent occlusive episodes. So if you look at the magnitude of the effect the therapy has, it’s profound.

All the other factors that you mentioned, percent F cells, fetal hemoglobin are all important. But what is most important is the durability of that effect, and the impact that has on patients lives.

And I think with time we’ll understand that relationship between percent F cells and fetal hemoglobin and that protection, but we really need to keep our eyes on what’s most important to patients..

Just a quick follow up to that.

Do you think that relationship is well enough understood right now snapshot in time or will be understood in the next couple of years enough that Hbf or some analysis of Hbf could be a potential approvable or accelerated approval, pivotal endpoint? Or will it really come down to VOCs or some other clinical aspects?.

VOCs are easy to measure. You just got a subtle laboratory based finding it’s with the patients report, I think that will remain the cornerstone of assessing effective therapies is unaffected, that provides patients particularly in this disease..

Got it. Bigger picture. Thank you..

Yes, so in terms of that, I don’t answer this, please clarify for me, but obviously, the crisper vertex guiding that they’re going to file sometime towards the end of this year, they’ve not shown as much of the dataset yet, at least as far as I know, in terms of any further updates, in particular, the registration directed study results, which would be expected.

And so time will tell in terms of how the discussions go once they file with the agency. In the meantime, we’ve also seen bluebird withdraw.

And so, it really becomes important for us to better understand the data that’s emerged, and we’ve presented today, but more importantly, as Rob alluded to the additional four patients with the change in the manufacturing process to see if that has any increased benefit in terms of the Hbf levels, percent F cell increases as well as the clinical outcomes for the patients.

And I think it’s really whether that profile looks competitive enough that will dictate how we take program forward..

Got it. Thanks..

Our next question comes from Gena Wang with Barclays..

Thank you for taking my questions. Two very quick ones. The first one also follow regarding the sickle cell program, what kind of clinical profile you will be thinking, the possible to keep in-house? Would there be crisper like profile? Or would that be better? The second question is regarding the base editors.

So I assume you use the MNAs, what about the IP part? Do you have a proper right to use that?.

Maybe why don’t you talk about sickle? And then Jason can speak to the base editors. .

Yes. So I hope you’re well, I mean, in terms of that data, they just sort of alluded to, I mean, I think it’s really going to be important to see the clinical profile in the four patients.

And it’ll give us a sense, roughly around the time that hopefully, we’ll see a little bit more of an update from crisper vertex, whether we’ve got a comparable product, or whether we’ve got a differentiated product. At the end of the day, these are personalized cell therapies, which means they need to be manufactured for the patient.

As I described, there’s 100,000 of the patients in the US, 30,000 of them are severe. And so even if there’s one competitor in the market, it’s going to take a long time to service the needs of the sickle cell communities, not only in the United States, but more importantly worldwide.

And so, we’ve got an attractive profile, that’s the same or differentiated through crisper vertex, we will do, as I mentioned earlier, what we need to do to either find a partner or look for novel ways that we can get these this met this therapy to patients..

Jason, can you help on the base editor question?.

Sure. Thanks, Sandy. Yes, regarding the base editor, this is a program that I’m incredibly excited about. We have a great team of molecular biologists, structural biologists that are continually innovating around our finger platform.

And they’re doing that on both the side of the zinc finger portion of the molecule, where we’re refining the specificity and accuracy of the molecules to target specific sequences. But they’re also doing it on the functionality side, right.

And so, moving beyond the core group of functionalities that we already have in our toolkit and nucleases, transcriptional, activators transcriptional regulators. We’re now exploring other new functionalities, including base editing, but also re-combinations and epigenetic editors.

And, we’ve got something in our base Editor program that we’re really excited about, we wouldn’t be moving forward if we didn’t think we had freedom to operate. So we’re pretty comfortable with the really unique architecture that we’ve developed.

And as Sandy pointed out, we think it offers some real advantages in being able to be deployed in a single viral vector, as well as taking advantage of the great specificity and accuracy aspects of the zinc finger platform..

Thank you..

Our next question comes from Patrick Trucchio with HC Wainwright..

Hi, good afternoon, everyone and congrats on the progress for this quarter.

So I just kind of have two questions on, I guess the first one to start off is what are some of the components that can result in the patient’s having elevated lyso GB3 level for Fabry diseases and how readily do these patients actually have increased lyso GB3?.

Patrick, can I make sure I understand your question it’s what Prathyusha talked to earlier that many patients proceeded those on ERT already have repressed by lyso GB3. And that the rare few naive patient will have elevated levels and those are the ones where we can see a benefit of our medicine and the lyso GB3.

And I think you asked are we screening for those patients, is that what you are asking?.

You will be screening for high lyso GB3 patients..

We’re delighted to take all patients with up Fabry and we take, we take three categories, we take the patients that are on ERT, we take what [Indiscernible] even those patients have been on for at least six months.

And we take the naive patients, and we’re not rejecting patients, if they have low lyso supplies for GB3 and we’re delighted when we find a patient. That’s a high level..

Great. And then kind of just like a follow up question. And so like, for the baseline of lyso patients, five and patients six, do you also see these increases in lyso GB3? Or is that something that we’ll see later on..

We commented on the lyso GB3 patients five and six..

Thank you for the question. We have not commented on both levels at this point in time. This is something that is part of that update that we can provide later in the year as we provide our clinical update..

Okay, great. Thank you for additional color..

We’re showing no further questions in queue at this time, I’d like to turn the call back to Aron Feingold for closing remarks..

Thank you all 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..