Good afternoon, everyone. My name is Gina Wen. I'm a Senior Biotech Analyst at Barclays. Welcome to Barclays' 27th Global Healthcare Conference. It is my great pleasure to introduce Sandy Macrae, Chief Executive Officer from Sangamo Therapeutics. Sandy, thank you very much for giving us this opportunity. Before we dive into the questions, maybe if you could give a quick overview of the company. Gena, it's a real pleasure to be with you and to be with Barclays here. Sangamo is a fascinating company. It's a genomic medicine company. It's a company that has the potential of two BLAs this year, in Fabry and in Hemophilia A. It's a company that will be moving into the clinic in the summer with the first ever Nav1.7 gene Therapy Repressor. It's a company that has evolved a fascinating capsid that at least two companies have now acquired, and we will then take forward into the clinic in 2026 for prion disease. Sangamo is based on a deep understanding of molecular biology and ability to use our zinc finger repressors and our delivery technology to focus the company as a neuroscience, neurology genomic medicine company. That we see is a future where we can make a great difference to patients. Great. Maybe start with your Fabry disease. Now we only have how many more weeks? Two more weeks in one Q? I know in the past you did say you will announce the deal for Fabry in one Q. Are we still on track? I know Monday you will have earnings. Should we still expect some announcement in the next two weeks? Deals happen when they happen, and we are in late phase and deep discussions with several parties. What they see is an asset that will have filing later this year, an asset where the last patient one-year visit is in April. Once that data comes, we will file for accelerated approval, as the FDA has guided, and file that in the second half of this year, allowing us to launch in the second half of next year. All of that is on track, and we continue to drive forward to make sure that the Fabry asset is as prepared as possible for the filing and launch. I think it is important to step back and remember that the decision by the agency to allow us to file with accelerated approval came in the very latter part of last year. Although Sangamo had prepared for a file three years hence, to hustle to get all the things done for a file this year is a major piece of work, and I want to pay great credit to my staff in the clinical and in the tech ops group for all the work that's been done. It complicates the business development discussions simply because there's so much for them to absorb in a short time. We still have confidence that this deal will happen, and we have some interesting parties that are very interested in what is an important asset. Let's just rehearse what they see in this asset. We showed that world data from 24 patients at one year, sorry, 23 patients at one year, 11 at two years, where there was a statistically significant improvement in the eGFR compared to their baseline. We believe that we can demonstrate a significant difference to the effect that would have been seen either without treatment or even on ERT treatment. What the agency sees that they find so appealing is it's an improvement in the renal function. It's an improvement in the SF-36. The SF-36 is that quality of life that the health payers will find very useful for valuing the product. It's an improvement in the pain score. It's an improvement in the Fabry false MSSI. It's testimonials from patients saying that they feel better. It's 18 patients that came into the study on ERT. All of them are off. As a whole, we've been treating patients for over four years now where the alpha-galactosidase A remains physiological or super physiological. We have been 18 patients off. The longest patient off now is over three years. This is really a remarkable medicine that will make an enormous difference to patients with Fabry. We hope in the hands of the right partner, we will be able to file it at the end of this year and launch it in 2026. Okay. Before I ask a specific question, I just want to confirm the deal term announcement was still happening first quarter? As I said, deals do not always happen exactly when you want. We want to make sure we do the right deal with the right partner. Okay. That means may have some delay on the announcement. It may move into the second quarter, but we're absolutely clear it has to happen soon. Absolutely clear because we need the funding to push forward our other projects. We're absolutely clear that it has to happen soon because with the pre-BLE meeting in the summer and then the filing by the end of the year, the partner needs to get involved in it. I want to reiterate what I said before. There are several people involved in important discussions with us, and I will make sure that deal happens at the right time. I think there's another reason. I think I previously talked about one Q is because you do only have a cash runway through one Q 2025. If the deal term, say, got a little bit pushed out to two Q, how will the cash situation be resolved? Gena, as we agreed before I came on stage here, we have our quarterly call on Monday, and we will talk about our cash runway on Monday. We also have, as you know, we've done two deals last year for capsids, and we're in significant discussions on another capsid deal. That allows us to achieve the runway that will allow us to have time to do the Fabry deal. Okay. Good. Now go back to Fabry, and I think you will have quite a lot of data in first half 2025. You will have 32 patient data, right? We did see the eGFR slope improve significantly from the initial, if I recall correctly, the seven and eight patient to, no, I think a 10-something patient to the 18 patient, significant improvement. That was additional patient data, and I'm giving the right dose. Should we expect the eGFR slope where we saw the last update will have a further improvement? I think we're adding more patients, and the signal is remaining. I've seen more than you have from the world data, and we're confident that it's not a signal, the effect. The effect on the eGFR remains. The effect on the renal function in these patients remains. From a Sangamo point of view, only two more patients, I believe, have got to get to the one year, which is happening in April. We are very confident that this benefit to the patient on their eGFR and on their renal function will remain. Okay. I think you already aligned with FDA on accelerated approval paths. Can you walk us through what they wanted to see in order for accelerated approval and also for the full approval? Accelerated approval is approval. I think it's worth restating that accelerated approval allows you to launch the drug and to commercialize it without restrictions. What the agency said very clearly is we would be able to get accelerated approval if the benefit to the patients on their eGFR was demonstrated in the 32 patients at one year. We're very much on track to show that. The agency did not require or did not ask for an additional study. I think people get confused about accelerated approval meaning an additional study. It doesn't. They may, at the pre-BLE meeting, ask for more data from the data package. I think it wouldn't be unreasonable for them to see all patients at two years. They haven't even required that thus far. We would be planning to make sure they're aware of that data, which is sometime in the middle of 2026. My understanding in the past was if you show two-year data, you could convert this to full approval. Is that correct, or was it my misunderstanding there? That will be a pre-BLA discussion about how they do it. In the minutes, and one of the very senior FDA advisors that we got to look at the minutes said he'd never seen such clear, concise recommendations from the agency. They said to get accelerated approval, we would be required to show one-year data for 32 patients. At that time, we'll also have 19 patients that will have two-year data. It is quite a body of data. The agency's next sentence was, "You may choose to submit two-year data to demonstrate the continued clinical benefit." We expect that they will show the two-year data when it is fully matured. I can tell you that the two-year data that we've seen so far continues to demonstrate a benefit to the patients. What we've also seen is that the one-year data predicts for each individual patient, predicts what their two-year data is. We are very confident both that we will show good one-year data and that if we are required to show two-year data, that should also be positive. When we look at the eGFR slope, that was super impressive. We're talking about three point something from previous less than one, right? It's very impressive. Did the FDA say something that's statistically significant in terms of the slope? It's more the endpoint, 12 months endpoint compared to the baseline. They have given us. Can we have the background noise turn off? The agency gave us we proposed how we were going to analyze this, and the agency agreed. We will analyze it both as the totality of the data to form the slope. It is not one point versus another. It is the totality of the data. We also will do appropriate meta-analysis to compare it to what happens normally in a Fabry patient and what is in the literature for Fabry patients on other forms of treatment. The agency has given us guidance on how we should look at those. I see. The BLA package, when you submit, what kind of data will be included in that? The totality of the data. That will be from the and including comparison to the natural history? We will compare it to what's in the literature for the natural history and what's in the literature and submissions from the various ERT treatments that are available. Okay. Good. That's very helpful. With the first half update, any other safety surprise we should be expecting? I think it's not the delight rather than the surprise is how well tolerated this is. We've now dealt with 32 patients and haven't had any safety events that were related to treatment. The patients do not require steroids, and they don't require either prophylactic steroids or steroids because of liver events. It truly is a really well-tolerated medicine. I think that will make it the medicine of choice for patients with Fabry. Clearly, patients who are on ERT would like to get off of ERT. This is also one I think will be available for patients as potentially the first treatment of choice rather than ever having to go on ERT. Okay. Good. Before I switch to your internal program, the other internal program, maybe quickly, any update on the hemophilia program? We're working with Pfizer to understand the data. I think people do not appreciate the volume of data and data sets that are involved in such a transfer. We've only recently started to see what Pfizer had generated. It's an enormous amount of data. I will say again, the clinical team at Pfizer did an excellent job. What we discover is they were days from submitting both the BLA and the MA days. This is a package that is ready and approvable, and we need to find the right way to take it forward. We've initiated a process, which has just started. We will work to see if there are people like us who feel that this should be an option for patients with Hemophilia. Any party that already show interest? We've had, I think, five or six companies have approached us. I'm not sure this will be a large pharma company. I think this is an opportunity for a specialist pharma company or a rare disease company. Okay. Very good. Given how long it takes for the Fabry deal discussion, I assume this also will take a pretty long time. By then, are you planning to complete transfer from Pfizer into your hand, then hand over to the new partner? That's a matter of discussion because that might be quite an inefficient way to do it. The ideal would be to transfer it from Pfizer to the partner. Those are discussions that we're having with Pfizer. Okay. Good. Okay. Regarding the Pfizer data, were you able to get access to all the full data package so far? There's a very clear contract about what they have to share with us. Okay. Good. Okay. Now, quickly on your Nav1.7 program. Yeah, which is very, very exciting. I know everyone wants to hear about the Fabry deal and the Hemophilia. The thing that I think is enormous credit to our scientists and our clinical team is that in very few months, we will start dosing Nav1.7 for neuropathic pain. This is a program that was developed before we had our own blood-brain barrier crossing capsid and uses AAV9 given intrathecally to deliver a zinc finger repressor to Nav1.7 to the dorsal root ganglion. Each part of that is something that has been shown to be effective in other hands. We know that intrathecal ensures that you get delivery to the spinal cord. We know AAV9 transduces the dorsal root ganglion. We know that the zinc finger repressor turns down NAV1.7. We know Nav1.7 is intimately involved in the pain pathway. From a kind of biological risk, this is a very logical thing to do. We will dose in a dose range finding study with three doses, each cohort having a placebo patient or a sham injection patient. We will hopefully accumulate data by the end of 2026. What is the initial indication? Idiopathic neuropathic pain, small fiber neuropathic pain. There are a lot of these patients out there, and they really struggle to find medicines that can control their pain. Okay. I wanted to hear your thoughts about the recent Vertex, the, what's that, blanking out, the LSR failure in terms of neuropathic pain, but there's a chronic pain and the failure. Any thoughts you're thinking or be questioning about Nav1.7 as a target? Nav1.7 and Nav1.8 hit different parts of the action potential. NAV1.7 is part of the initiation, and the propagation of the action potential is Nav1.8. We could have chosen either because for us, it's simply a bit of DNA that we would be binding to. When we spoke to, when we took really serious advice on this, they said that they thought Nav1.7 was, a, the most important target to go for, and also one that nobody has been able to drug with a small molecule. That's simply because with a small molecule, there's similarity to other channels, and you end up with off-target cardiac effects. Just to reiterate again, because I know you understand this, but the zinc finger repressor is aimed at the DNA in the promoter section of the channel. That is a unique piece of DNA that does not look like any of the other sodium channels. We have already started site initiation, and we look forward to dosing that in the middle of the year. Any thoughts on the initial dose and what you are looking for? We know exactly the initial dose. We have gone for a dose that looks like it should be lowest therapeutic effect. We have three dose cohorts, and we will share details of that in the future. Okay. What could be the initial measurement you'll be looking for? That would be just pain score or? I mean, pain scores are the most important. These patients' lives are dominated by their pain. Would we use this in acute pain? No, because in acute pain, there's a whole variety of other things that you could do. This is for people with intractable pain whose days and nights are dominated by that pain and who really don't have any other alternative and would love to stop taking some of the opiates or the channel blockers or the baclofen or all the other things that they take to try and control this pain. Is it a 12-week measurement? We'll be measuring the response over the first 12 weeks, but we intend to follow this out hopefully for a year to show continued benefit because this isn't for a short-term benefit. This is for long-term benefit to the patient. Given the noise of the pain score measurement, I know could that be different from the traditional phase I study where you're thinking about one cohort as a placebo so that you can manage the noise? Each cohort will include a placebo, and then that will generate in effect a placebo cohort. I often get asked about the placebo in this. These are patients with dreadful intractable pain. This is a medicine that should switch off the pain signaling and should, if it is a valuable medicine, have a dramatic effect. In addition, the placebo effect is maximized when you're taking the tablet every day. You're reminded that you're taking an active medicine. This is a case where the patients will be dosed, and then if you take the 12-week point, for example, it's 12 weeks since they had the intervention. And so the memory of what they had may be less placebo-like than a daily tablet. I see. Okay. I think more of the scientifically, I think do you think it makes sense to try to target both Nav1.7 and then Nav1.8 and giving you have an easy capability of doing something? Yeah. One day, that might be an interesting experiment to do. One of the real advantages of zinc fingers is how small they are. We could multiplex three zinc fingers into a single AAV. I think it's important to start with Nav1.7 and see the effect and then decide what needs to be done after that. Even today, one of the investors who was speaking to me was remarking this is the initial indication, but there are so many other things that you could expand as to trigeminal neuralgia as one obvious one. We are very excited to see the result of this for patients dosed. Maybe quickly go back to the SFN study. What kind of baseline medication you will allow a patient to take? I think we have to accept that these patients need their medicines because their lives are so hard and miserable. This will be on top of their standard of care, and there will be rules about what that can be. We will also be monitoring rescue medicines because we can't force the patient to be with pain when that's unnecessary. Will you normalize the rescue meds and also the baseline, the therapy? Do Do you try to? We will be very thoughtful in the baseline medicines that are allowed to try and make the signal as clear as possible. I just want to say again, this is a once-and-done medicine that will give patients long-term benefit. For that to be a useful medicine, it has to be an effective and safe medicine. We believe that we will see a clear signal in this. If you and I are trying to shift between the placebo, this probably is not an effective medicine. Good. We are on time. Thank you very much. My pleasure.