Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. So great pleasure that I'd like to welcome Sandy Macrae, the CEO of Sangamo. Thanks so much for joining us today, Sandy. We're going to do a fireside chat. Maybe for those who are new to this, the Sangamo story, if you can provide a one-minute intro into your pipeline and mention some of the key catalysts in the next 12 months. Thank you, Maury. It was fascinating to listen to the previous talk, Catherine from Chroma, as she talked about her preclinical data on repressors, and we've just done a deal with them, so we're close to that because they've chosen zinc finger repressors as the way forward. Because once you're in the clinic, all people want to hear about is the clinical data, and that's the thing that we've executed on in, in my time at Sangamo. So if I look across the spread of our clinical activities, we have hemophilia A with Pfizer, which is guiding to a BLA next year that will lead to $220 million worth of milestones and then 14%-20% royalties from Sangamo. We have our Fabry program, where we have got best-in-class, first-in-class, only-in-class data. There was a Fabry meeting on Friday, the National Fabry Disease Foundation, and three patients came up to my project leader and said, "You know, we've got your gene therapy inside us. We feel better. I can go to work. I can go out for a walk. I was never able to do that on ERT." We've dosed publicly 22 patients, five publicly are off ERT, and all of the patients that are off ERT have stayed off ERT. They feel better. Their renal function looks good. Their SF-36 looks good. This is a medicine that works and works beautifully, and we now have a path forward that we feel we've agreed with the agency to take this into phase III. And then if I go further right, we have a sickle program where we've dosed publicly seven patients, and the data in the patients on the improved methodology, we have three so far on that, looks really good. It's as good as anything that anyone has shown. But more importantly, what we've decided is manufacturing is essential for that, and we've come up with a manufacturing process that we think will drop the cost of goods and lead to access to medicine. And finally, on my kind of clinical spread are the CAR- T regs. We're the only CAR- T reg company in the clinic. Others are trying, and, and we hope they will get there because it's an important area. We've dosed three. The fourth will be dosed in this quarter. But we have a way now that we can get to the highest dose quickly, and we hope by the end of the year to show you data from the first biopsy and also to show you, tell you how we'll get to that higher dose. The higher dose is 18-fold higher than the starting dose, so we really have a huge range of doses. You start carefully, you start low because it's a completely new technology. But then thinking about the Chroma piece that we just heard about, I want to make sure that you keep thinking about the essence of Sangamo, which is the zinc finger platform, the zinc finger repressors, because a lot of what Katherine said was correct. Nucleases have their use, base editors probably have a use, but the advantage of repressors is control without double-stranded breaks, single gene control, and repression. And if you can deliver, you have a fantastic solution to many things. So we showed the ASGCT multiplex editing of using zinc finger repressors that would allow you to create allogeneic cells. But the focus of the company moving forward is our neurology platform, and that's because in the CNS, where cells divide slowly or don't divide at all, there's an advantage to repression over double-stranded breaks because you need the repair mechanism to make it to for the double-stranded breaks to be carried forward. We have programs in NAV1.7, which will be in an IND next year for pain, and then we're guiding for the following year for IND for prion disease, where in the mouse model, the mice live a normal old age once they've been treated with zinc finger repressors of prion. We have a very active capsid program. We are evolving capsid specifically for delivery to crossing the blood-brain barrier, and it's absolutely true that editing is something we all understand. It's about delivery now. And if we are able to show and convince you all that we have that blood-brain barrier crossing capsid, opens up a whole range of diseases. We have zinc finger repressors for tau. We have ones for synuclein. We have a whole range of diseases just waiting for that capsid, and we believe we will be the only company with capsid and cargo, and we believe the value is in this. Yes, it'd be great to do capsid deals like some of our friends like Voyager has done. Yes, it'd be great to say you've got ways to repress a gene, but if you have both of them, that's the future of genomic medicine for the, for the CNS. This is an enormously exciting time for Sangamo. Clinical delivery, cutting-edge science, drugs that make huge differences to patients, and a science and technology that will lead us to the future. Got it. Yeah, I think that's a great summary and overview, and it tells us there's a lot going on on multiple fronts, at Sangamo. Definitely want to ask some questions about the clinical programs. Yep. With Fabry, with ST-920, you've gotten written feedback on your proposed phase III, and you noted the phase III will likely take place in two studies across naive and pseudo-naive and ERT patients in order to maximize potential for a broad label. Based on the total feedback, you don't anticipate needing to run a head-to-head versus ERT. Can you elaborate on what gives you confidence that you won't have to run this head-to-head study? And what are scenarios for what the bar for success would be? So I want to make sure I speak carefully here and address your question. Fabry has a range of patients with different needs. There are patients that are newly diagnosed or diagnosed through a family member that are naive. There are patients who are pseudo-naive, and according to definition, that's six months off of treatment. And then there are patients that are on ERT. ERT means you go to the clinic every second week. You're in the clinic for 3-7 hours, and then two weeks later, you go again, and then two weeks later, you go again, and then two weeks later, you go again. And I know for busy people in the room, that just does not appeal, and the patients don't like it. And so that's why we feel that what we want to try and describe is, what is a universe of studies that address as much of that population as possible? Companies like Sangamo have to choose wisely the studies they do and the ones they can afford. Multinational companies would go for the broadest label in the shortest time. And so that's the dynamic. And we, we've said publicly that people are talking to us about our Fabry program because they're interested in it, and it might be a way for us to get it to patients quicker. What we think, what we believe we've heard from the agency is for the naive, pseudo-naive population, you don't need to do a comparison against ERT. I really do feel for an... If I was advising physicians to use it in ERT patients, I'm sure they would want to see data where it's a patient who is on ERT that then comes off of ERT. So for that label, I think it's not just a regulatory requirement. Doing something with that involves experience in ERT, then switching it off, is also useful for patients and for physicians. Mm-hmm. Makes sense. That makes sense. And, you said you plan to request additional clarifications prior to submitting the proposed phase III as early as the end of this year. Can you elaborate on what you're trying to get clarified? And have you had any recent conversations, and what progress has been made? So when you go through that process with the agency, you're allowed clarifying questions. We've done that. We've got the information back from them. And then it's a matter of deciding how you advance with that. And we're still guiding that we will try to get the phase III protocol completed and initiated by the end of the year. Got it. And, I believe you've also said that you can give additional details, potentially at your third quarter update, which I assume is going to be early November and prior to potential submission. What could you tell us at that point in terms of, trial design or other details? We'll tell you as much as possible. We've got great data, we believe, for Fabry disease. It really makes a difference, and it's finding ways to capture that we don't have abstract conversations about alpha-G al, and that we can share with you as much as the patient benefit as possible. And then we will eventually, this trial will be published, and you'll be able to see it on ClinicalTrials.gov and see all the details of it. But we want to guide you as carefully as possible on the journey ahead. We feel we have that journey in our sorted in our head. We know the way we're going, and this is important for patients with Fabry disease. Makes sense. And, you've mentioned getting a broad label and getting to as many patients as possible and how Sangamo could potentially not do that on their own. So, how do you think about partnering this program? Is partnering something you want to do before you figure out the ultimate trial design, or would you do that afterwards? And, yeah, I guess maybe talk about timelines there. Therein lies the joy of partnering, that partners want the program as de-risked as possible, want to understand the way forward. Partners will also want to do it their way because they will have their interpretation of what it is, and so it's always an interesting dance. Partnering, you see the moment the announcement happens. It's six months or a year of discussions usually that precede that. So, we want to do the best for patients with Fabry. We feel we've got a medicine that makes an enormous difference, and we have a responsibility to try and get it there. Got it. Do you think there's a particular data set that's more important to a potential partner? We've seen a lot from the phase I, II so far. They're interested in everything. They're interested in... You know, when you do something like this, a late-phase asset, you want to make sure it works. You want to make sure it's safe. And I think we have data that's compelling for that. And so it's just a matter of sharing it as it comes. Okay, makes sense. And, for patients on ERT versus naive or pseudo-naive, you said that you might be able to start the latter trial sooner and that the trial would be easier to get going. You also said you could potentially expand the phase I/II for patients that are on ERT and conduct an ERT withdrawal study. We're looking at all kinds of options because we feel we want to move this forward as quickly as possible. Got it. Okay. Let's see- But it's important to realize that if you look at the landscape for gene therapies for Fabry disease, Sangamo is the only company in the hunt here, and we're the only one that has treated a significant number of patients. We're up to 22, we've said publicly. The patients are doing very well. The patients are seeing benefit. 4D MT, Freeline, AvroBio, Amicus, they've stopped as far as we can tell. So this is the gene therapy for Fabry disease that we have. ... Makes sense. And, for the next update from Fabry, could that be at World in February? I guess, when could that update be? And- That's the next big conference. Okay. We have quarterly calls on the way, but that's the next big conference. Are you saying how many more patients or biopsies we could see that update? We'll tell you when we tell you. Got it. Okay. And let's see. Let's move on to CAR- T reg then. Please. So with this program, you're treating patients with kidney transplants, mismatched by HLA status. First, can you tell us roughly how you see the market opportunity with numbers of patients and the unmet need with the current standard of care? There hasn't been anything developed in renal transplant for a while. Patients take immunosuppressants that have consequences in their long-term health. Patients would love to have something that, that tolerizes them to the transplant, and we're done. The renal transplant study is a great study because the transplant is biopsied. There's only one place the antigen is, so from a kind of technical point of view, the study's a good one. Patients are enrolled based on HLA-A2 mismatch, and all renal transplants are HLA matched or, or are HLA typed, so you know which patient's got the mismatch. About 20% of them, just over 20%, has an A2 mismatch. We do the apheresis, we do the manufacturing, they then get their transplant, and then, three months later, and that's simply because we felt it was prudent to let the transplant wound heal, we then give them the CAR-Treg, which has got HLA-A2 CAR in it. The only place it can go that that has got A2 in it is the transplanted kidney. So that's the premise, and we're at the very lowest dose, and we've got 18-fold higher to go yet. And we will. Over that time, we will talk about biomarkers, we'll show some biopsy data, and then, the investigators know that they can start to withdraw the therapy. In polyclonal Tregs, they were able to withdraw the therapy in a number of patients. We hope this will be better because it's specific for the HLA mismatched kidney. This is a live cadaveric... Sorry, this is a live transplant, and of course, if that's successful, we could look at expanding it into cadaveric transplants. So we feel there is an opportunity for this to teach so many of the other programs we've got, and also to give an opportunity for the right-- We're not a transplant company, but for a transplant company, this could be a very interesting asset. Got it. Behind that, we have CARs for IL-23R for inflammatory bowel disease and MOG for multiple sclerosis, and that will mean an IND in 2024 for one of them and 2025 for the next one. Yes, and those are pretty big opportunities for those- Yeah ... two indications. What's the status of those for MS and IBD? I'm going to France on Saturday to see them, to see the team there, to look at them, but they're making good progress, and we feel we have a package of data that should be able to allow us to fulfill those INDs. Got it. Okay, and presumably some of the data from the kidney transplant program could be included? Well, you know, if it's, if for nothing else but saying CAR-Tregs are safe, will give great comfort to the patients, the, the physicians treating MS patients or inflammatory bowel disease patients, because that—this is a first in our industry. Other—there's, I think, 15 other CAR-Treg companies that are trying to get there, and what they're discovering is it's something about the science, but it's largely about the process development and the manufacturing, which the team in Valbonne do so very well. It's about owning your own manufacturing so that you can understand how that's done, and it's about having experience in putting together INDs. We also have an editing capability for them. So when we move from autologous to allogeneic, they're perfectly equipped with the Sangamo editing capability to take us to allogeneic therapy. Got it. And for initial data for TX200 in the kidney transplant setting, what could we expect for that update? Maybe talk about whether you're going to have biopsies and other biomarkers that we should be focusing on. We will show you whatever date we can, and we've said we'll do that by the end of the year. Got it. And so that's going to be three patients from cohort one. There's three patients in cohort one. There's one, another one being dosed in cohort two this quarter, and then there's a series of patients that we have planned. It takes so long for these—because you've got to base everything around the transplant, that you have long line of sight of when the patient is going to go through their transplant. And so we're able to speak, more, logically about the progress of the study. Got it. And for this initial dose, you mentioned that it's much lower than where you plan on going with dosing. What could you expect as far as the clinical benefit goes and potentially being able to remove immunosuppressants? Wait and see. Sounds good. And, let's see. For partnering for CAR-Tregs, talked a little, a little bit about MS and IBD. Could those programs potentially be partnered at some point? We're always talking to people about partnerships. We're always interested in finding ways to get our medicines to patients as quickly as possible. We are a company with limited resources and great and multiple assets that are working really well, and therefore, that's the only real solution for us. ... Got it. And for hemophilia A, this is a program that's partnered with Pfizer, and you probably can't say a whole lot about it. I can't. There's very little I can say other than Pfizer keep guiding us, that they are, the study's going well, and the BLA is planned for second half of next year, with a launch the following year, which, you know, that's a first for Sangamo. Yeah, got it. And there's also a competitor launch underway right now with Roctavian from BioMarin. What can you say about learnings from that launch, and they're pricing their, their drug at $2.9 million? I guess any perspective on that, that you can- So I don't want to comment on the price, but it's always easier. You know, Sangamo so often has been the first company to do things, so it's quite nice to be second in this one and watch from them and learn from them. And I'm sure Pfizer will learn a great deal from how that launch goes, and I trust Pfizer to launch it well. Got it. And, you've talked about potentially monetizing this program, which includes the 14%-20% royalties and around $225 million of milestones from now through commercialization. Is this likely an event that occurs post Pfizer's mid-2024 data update, or could it happen earlier? The longer we hold on to these milestones and royalties, the more valuable they are. The sooner we do it, the more discounted it is, and so that's just a choice we have to make, we can make as a company. Makes sense. Wanted to talk about NAV1.7. This is your lead preclinical program, which is a ZF repressor. You've mentioned IND for second half of 2024 for this one. Can you talk about the rationale for using a gene regulation therapeutic in pain, and maybe on what the ideal repression of NAV1.7 should be to get to a normal pain, based on your preclinical data? Yes. So zinc finger repressors exist in all of us. They are how we control our genes, so they're one of the commonest transcripts in all of our bodies, and they land near the promoter initiation site and control how much of the gene is expressed. With our technology, if you give us a target, and I'm sure we'll be doing this for our friends at Chroma, we will give you hundreds of options, and in amongst them, we will choose the one that gives you exactly the amount of repression you want with single gene specificity. It's very beautiful. It's exquisite science. And by doing that, we can choose a part of NAV 1.7 that doesn't look like any other channel, and therefore has none of the adverse events that people worry about with these channels. I challenged the team to come up with a neurology target that was available with the existing delivery, and that's why we went for NAV1.7 with an intrathecal delivery with an existing vector. Because at that point, we were still early in our blood-brain barrier crossing capsid. Future targets, I would hope, will use a blood-brain barrier crossing capsid that we will evolve and will take us into the CNS. But this is... We're careful to call it neurology because it's not central neurology, it's a DRG. So we target the DRG, which is one of the pain gating sites within the spinal cord. We have shown in mice at various doses that we get really good pain relief in the kind of classical pain models in mice. We have done ex initial studies in the non-human primate and showed that that's safe and the histology looks good. And now we're going into the final IND-enabling studies to enable us to do that IND in the second half of next year. Got it. Makes sense- But we're not talking about... I, you know, I know that, Vertex has got their own NAV1.8, and their initial studies in the New England Journal of Medicine, you know, were encouraging in bunionectomy and stomach surgery, I think it was. That's not the population we're going for. We're going for people that have got intractable pain due to small fiber neuropathies that really just can't live with the pain they have. And for that, I think a gene repression that hopefully is once and done and turns right down the, the pain is an important solution for them. Got it. And, yeah, for competitors, is there anything else you want to highlight as far as differentiation goes, or what you could learn from other competitors out there? No, because we're the people that understand the zinc finger repression and activation pathway. We have repertoires of zinc fingers. We have a really advanced bioinformatics group that helps us do it in silico now, largely. And we can target any gene and turn it off and increasingly turn it on as well. And it's just a matter of choosing the targets and then deciding what are the things that we can do and what are the things that we should partner as we've done with Chroma with other people. I cannot say sufficiently what if we crack the blood-brain barrier crossing capsid, how that opens up a whole range of things. Then we had to deal with Biogen for tau, for Alzheimer's. Beautiful. It worked beautifully. They just didn't have a capsid that they felt they could use for Alzheimer's. If we, if we crack that ourselves at Sangamo, we have tau, we have a capsid, that's an incredibly exciting way forward. Makes sense. And, for NAV 1.7, anything more you're saying about the sort of IND-enabling studies you're doing or anticipate having to do prior to getting the green light from FDA to start a- They're all, they're all very standard studies, and we have them underway, and we believe we will complete them. ... Got it. Okay. And you've talked about the, the ZF repressors and activators. How do these compare to other gene editing programs out there? Maybe talk about how this is superior or what are the advantages it has versus other programs. It's very rare for anyone to have both and put them in a trial and test them against each other. So when a CRISPR company comes to us and asks for a repressor, that's a nice moment. And at ASGCT, there was a number of people talking about how particularly for the repressors, the zinc fingers are simply better. They're smaller. They manage to get under the chromatin. I'm being a bit basic in my science here, but they're able to access chromatin pieces of DNA. You can multiplex them. We could put three of them in a lentivirus, and you can then get an array of them and choose the best one. So we really feel for the field of repressors and enhancers, we have the technology that other people now want to access. Makes sense. And you've talked about the capsid and cracking the code with the capsid, too. Your second program is prion disease, and you've shown great mouse data with that program. And you recently announced a deal with Voyager to use one of their AAV capsids to optimize brain transduction. And then, yeah, maybe- We felt an urgency to find a capsid. Now, we may find a capsid, and that would be an interesting moment. But 500+ patients die each year from prion disease. It's usually a sporadic thing. Occasionally, it's acquired, and for a poor group, for a really, difficult group of people, there's a hereditary form. The mouse data is incredible. The mice, if you infect them with prion, die on day 160, almost on the dot. If we treat with the zinc finger repressor to prion, either. And this is intravenous crossing the blood-brain barrier, either before they get prion, which is the easier form, but even after they've been infected with prion, they live normal lives, absolutely normal lives. The prion is prevented from exponentially growing, and the mouse is able to survive. We feel that this is an urgency for us to get it to patients because these patients are dying. They die within a year or a year and a half once they show the signs of prion. If we could do this, this feels like a very urgent thing to do, and it also feels like the kind of thing you could go and talk to the agency about getting accelerated approval of some kind. What are next steps for the prion program, and...? We're working on the Voyager capsid. We have our own capsid work going on in parallel, and we are doing the IND enabling studies. Currently, we're guiding that's a 2025 IND. Got it. Okay. I think we're almost out of time. Maybe to close out, if you want to talk about current cash runway and cash burn and some of the key catalysts ahead over the next 6-12 months that investors should focus. These are difficult times for biotech. Everyone needs more cash. Everyone's looking at ways to fund the company, particularly if you're a clinical company. You know, that's when the spend increases exponentially. I know we need to simplify our story. I know we need to make choices about what it is that Sangamo focuses on, which is why you can hear me today talking as much as possible about our our neurology CNS programs. I also know that I have a responsibility to the Fabry patients that came up and spoke to us and the Treg patients of the future. I need to find solutions for them, and I need to find ways to fund that or part of that, so as we can make sure our science gets to patients. Makes sense. Sandy, thanks so much for joining us today. It's great speaking with you. Always a pleasure. Thank you.