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Good afternoon, and welcome to the Sangamo Therapeutics Second Quarter 2025 Teleconference Call. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker today, Louise Wilkie, Head of Investor Relations and Corporate Communications. Please go ahead.

Thank you. Good afternoon, everyone. Thank you for joining us on the call today. On this call are several members of the Sangamo executive leadership team, including Sandy Macrae, Chief Executive Officer; Nathalie Dubois-Stringfellow, Chief Development Officer; and Prathyusha Duraibabu, Chief Financial Officer. Slides from our corporate presentation can be found on our website, sangamo.com, and under the Presentations page of the Investors and Media section. This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements relating to Sangamo's cash runway, Sangamo's plans to obtain additional capital and its ability to continue to operate as a going concern, the therapeutic and commercial potential and value of Sangamo's product candidates and technologies; Sangamo's ability to establish and maintain collaborations and strategic partnerships, including for its Fabry disease program, the anticipated plans and time lines of Sangamo and its collaborators for clinical trials, clinical data presentations and releases, regulatory submissions and regulatory approvals, upcoming catalysts and milestones and other statements that are not historical fact. 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 in our annual report on Form 10-K for the fiscal year ended December 31, 2024, and our quarterly report on Form 10-Q for the fiscal quarter ended -- sorry, June 30, 2025, and subsequent filings and reports that Sangamo makes from time to time with the SEC. The forward-looking statements stated today are made as of today, and we undertake no duty to update such information, except as required by law. Please note that all forward-looking statements about our future plans and expectations are subject to our ability to secure adequate additional funding. Now I'll turn the call over to our CEO, Sandy Macrae.

Thank you, Louise, and good afternoon to everyone joining the call today. This quarter, we made important advances across both our clinical and preclinical pipeline. In June, we are happy to announce the positive top line results from our registrational STAAR in Fabry disease, taking us one step closer on the path towards potential approval of this promising treatment for Fabry disease patients. This month, we also became a clinical stage neurology genomic medicine company with the initiation of our first clinical site in the Phase 1/2 STAND study in chronic neuropathic pain. This is an important achievement, that means we are on track to generate clinical data for this program anticipated towards the end of 2026. Finally, earlier this quarter, we held a productive meeting with the U.K.'s Medicines and Healthcare products Regulatory Agency, or MHRA, for our preclinical prion disease program and are on track for a planned CTA submission for this program as early as mid-2026. I'm proud of the progress and proud of my Sangamo colleagues who continue to work tirelessly to advance our pipeline while operating in such a challenging environment. Let me now hand directly to Nathalie Dubois-Stringfellow, our Chief Development Officer, to provide more context on these important programs. I will then close the call by summarizing the key takeaways from this quarter, and we'll put these updates into perspective. Nathalie?

Thank you, Sandy. First, I am pleased to share details of the recent positive top line results from the registrational Phase 1/2 STAAR study evaluating isaralgagene civaparvovec or ST-920, our investigational gene therapy for the treatment of adults with Fabry disease. Following a single dose of ST-920, a positive mean annualized estimated glomerular filtration rate or eGFR slope of almost 2 was observed at 52 weeks across all 32 dose patients in this study. The FDA has agreed that mean eGFR slope will serve as the primary basis of approval under the accelerated approval pathway. Furthermore, a positive annualized eGFR slope of 1.7 was observed for the 19 patients who have achieved 2 years of follow-up. I want to take a moment to reflect upon this important accomplishment. As a reminder, the average untreated patient, Fabry patient experiences an annual decline in eGFR slope of minus 3 or minus 4. Achieving a positive mean eGFR slope across all 32 dose patients after 1 year and across the 19 patients who have reached 2 years is remarkable. As recommended by the FDA, we plan to compare the annualized mean eGFR slope of ST-920 with approved treatment for Fabry disease by performing a meta-analysis of published studies. According to observational studies, other marketed treatment options such as Replagal, Fabrazyme and Galafold show a decline in annualized eGFR slope of minus 2.2 to minus 0.4. Key secondary endpoints in the ST-920 study were also positive. We continue to see strong durability in the study with elevated expression of alpha-Gal A activity maintained for up to 4.5 years for the longest treated patient and plasma lyso-Gb3 level that remain generally stable following the withdrawal of enzyme replacement therapy or ERT. We are excited to share for the first time a stabilization in cardiac endpoint, including a stabilization in cardiac function and morphological and biomarker data in the 32 patients with 52 weeks of follow-up. Measurement by MRI, including left ventricular mass, left ventricular mass index, left ventricle myocardial global longitudinal strain T1 and T2 mapping, end-diastolic; and endsystolic volume remained stable over one year. Furthermore, left ventricular ejection fraction measured by echo as well as cardiac biomarker such as troponin and NT-proBNP, have remained stable in all patients at one-year of follow-up. These data are striking, particularly given that cardiac function in Fabry patient tends to decline over time and is the leading cause of death in Fabry disease. Patients demonstrated a range of other clinical benefit, including improvement in disease severity reported in the first MSSI age- adjusted score and statistically and clinically significant improvement in the SF-36 quality of life scores, including a change of plus 15 in the role-physical score, plus 10 in the vitality score and plus 9 in the bodily pain score at 52 weeks compared to baseline. Statistically significant improvement in the gastrointestinal symptom rating scale compared to baseline were also observed. I would like to particularly emphasize that ST-920 has been well tolerated in the study. The majority of adverse events were grade 1 or 2 in nature without the need for preconditioning. There was no safety-related study discontinuation or death. We believe that the totality of this compelling data demonstrate the potential for a single dose of ST-920 to treat the underlying pathology of Fabry disease and provide meaningful clinical benefit above current standard of care. ST-920 has shown the potential to transform the lives of patients, and we have observed additional clinical benefit in some, including the reduction and elimination in pain medication usage and the resumption of sweating, which has enabled these patients to perform physical task and exercise they were previously unable to do. Following dosing with ST-920, all patients who came in the study on ERT were able to safely withdraw from ERT with one patient now off ERT for more than 3 years. In so doing, this patient have already avoided more than 1,000 biweekly ERT infusion, each of which can last up to 6 hours. What a transformation in the life of these Fabry disease patients. Since the top line readout in June 2025, a physician has decided to resume ERT for one of their treated patients who had withdrawn from ERT. This patient who received ST-920 more than 2.5 years ago, maintained supraphysiological level of alpha-Gal A activity and their lyso-Gb3 levels were generally stable as of the top line readout date. All of the other 17 patients who began the study on ERT and have withdrawn from ERT continue to remain off ERT as of today, with many experiencing benefit of ST-920 over and above what they were experiencing with ERT alone. All 32 patients have transitioned in the long-term follow-up study and the STAAR study is now complete. We continue to engage with the FDA ahead of our anticipated BLA submission under the accelerated approval pathway planned for as early as the first quarter of 2026. We are also looking forward to sharing additional clinical data at the 15th International Congress of Inborn Errors of Metabolism or ICIEM2025, taking place September 2 to 6, 2025, in Kyoto, Japan. Before we move on and on behalf of our entire Fabry team at Sangamo, I want to take a moment to sincerely thank the patient and investigator who have participated in the STAAR study. Your dedication and commitment have been invaluable as we advance this treatment for such a debilitating and multifaceted condition towards registration. Thank you. Turning now to our neurology pipeline programs. As Sandy shared, this quarter, we became a clinical stage neurology genomic medicine company with the initiation of our first clinical site in the Phase 1/2 STAND study, evaluating ST-503, our investigational epigenetic regulator for patients with intractable pain due to idiopathic small fiber neuropathy or iSFN. This is an important milestone for Sangamo, and we're excited to be identifying patients in our first-ever neurology clinical trial. I want to thank everyone involved. We anticipate activating at least eight other clinical sites in the coming months, which we believe will further accelerate patient enrollment. We expect to dose the first patient in the fall of this year and anticipate having preliminary proof of efficacy data in the fourth quarter of 2026. Our preclinical data for this program is compelling. By directly targeting the SCN9A gene, ST-503 has shown to precisely and potentially reduce the expression of Nav1.7 sodium channels in sensory neurons in animal models and significantly reduce pain hypersensitivity following a single intrathecal administration. ST-503 has been well tolerated in nonhuman primate with no off-target effect observed. And we plan to present updated nonclinical data at the 9th International Congress of Neuropathic Pain, taking place September 4 through 6 in Berlin, Germany. Finally, I am pleased to share progress in ST-506, our epigenetic regulator for the treatment of prion disease to be delivered intravenously using STAC-BBB. Earlier this quarter, we held a productive meeting with the U.K.'s MHRA and aligned on the planned nonclinical safety study as well as the proposed clinical study design. We appreciated the collaborative nature of the discussion and their acknowledgment of the urgency to find a treatment for prion disease patient. We were also extremely proud to be selected to present during the prestigious Presidential Symposium at the recent ASGCT, Annual Meeting in New Orleans, where we showcased our potent combination of epigenetic regulation and capsid delivery technology in prion disease, including the profound survival benefit we observed when administered to post symptomatic mice. In addition, we described the sustained brain-wide suppression of prion protein expression in both mouse and nonhuman primate model, supporting the potential of ST-506 as a onetime therapeutic approach for prion disease. We have completed dose-range finding study and are preparing for the GLP tox study ahead of an anticipated CTA submission expected as early as mid-2026. I would like now to hand it back to Sandy for closing remarks. Sandy?

Thank you, Nathalie. To close, we made strong pipeline advances this quarter. Firstly, we announced positive top line results from the registrational STAAR study in Fabry disease. We observed a positive mean annualized eGFR slope at 52 weeks across all dose patients in the study, which the FDA has agreed will serve as a primary basis of approval. Beyond renal function, we are pleased to observe a range of positive secondary endpoints and broader quality of life data, including a stabilization in cardiac endpoints. And importantly, ST-920 continued to be very well tolerated in the study without the need for preconditioning. We continue to engage with the FDA ahead of the planned BLA submission expected as early as the first quarter of 2026. Secondly, this quarter, we became a clinical stage neurology genomic medicine company with the initiation of the first clinical site for the Phase 1/2 STAND study in chronic neuropathic pain. We expect to dose the first patient in the fall and anticipate having preliminary proof of efficacy data in the fourth quarter of 2026. And thirdly, we held a productive meeting with the MHRA for ST-506 in prion disease ahead of an anticipated CTA submission as early as mid-'26. Moving now to broader business updates. Earlier this quarter, we completed an equity offering that we hope will bridge us to an anticipated Fabry commercialization agreement. Our current cash runway is expected to fund our planned operations into the fourth quarter of '25. And we remain highly focused on our critical task of securing a Fabry commercialization partner in the near term. We continue to advance business development negotiations for that potential Fabry commercialization agreement and are also engaging in broader business development discussions across our Sangamo pipeline and platforms, including our MINT platform. We remain focused on solving our long-term funding needs in order to enable us to advance our promising neurology genomic medicine pipeline. Operator, please open the line for questions.

[Operator Instructions] The first question comes from the line of Maury Raycroft of Jefferies.

This is James on for Maury. Congrats on the progress. Just to start off, has the team already held the pre-BLA meeting with the FDA to discuss the potential path to approval using the 1-year eGFR data as a predictor for the 2-year eGFR benefit versus having to confirm the clinical benefit with 2 years of data from all patients. And if you had that meeting, could you share any takeaways from that discussion? Also, how important is the FDA alignment on the 2-year eGFR prediction in the context of the ongoing partner discussions? And I have a follow-up.

Thank you for the question. So let me just restate, we held a meeting last year with the FDA where they agreed on accelerated approval. And at that meeting, they said that we could achieve accelerated approval with 1-year eGFR data and included a clause in it that said we might wish to submit 2-year data when that was available. We currently have 32 patients at 1 year and 19 patients at 2- year. And the 2 data sets are very similar and complementary. We have not yet held our pre-BLA meeting because it's not the time to do it yet and have plans in place of when and how we're going to do that. The pre-BLA meeting is very much an operational meeting where you agree with the agency on what it is that you have to do to fulfill the BLA requirements, what sections, how it has to be presented, et cetera. We have no expectation that the agency will require anything other than the 1-year data for accelerated approval. And we are sure that we will end up providing them with yearly updates as these patients advance. So just to remind you all, the latest -- the earliest patient is now 4.5 years out, and the data looks very consistent and very stable.

Got it. And then just another one. For the upcoming presentation SSIEM, what additional insights should we anticipate? Can we expect any details at the conference regarding the meta-analysis or new baseline characteristics such as proteinuria? Also, will you show individual eGFR trajectories or alpha-Gal levels for each patient or just the average?

So I'll pass this on to Nathalie. But before I do that, I would say it would be really unusual in a patient data set of 32 patients where it's comparing the body of patients before compared to after to dissect out and show each individual patient. So we don't intend to show that at the presentation -- at the meeting in Japan. We may do that as part of a larger publication that we're working on at the moment. Nathalie?

Yes. Thank you, Sandy. We look forward to sharing additional clinical data at the ICIEM conference. We plan to present the top line data with additional details compared to the press release issued back in June. We encourage you to review the data presented at ICIEM that will also be available in our website once the embargo has lifted.

But Nathalie, our plans would be to say a little more about this.

Absolutely. Absolutely. Yes. There will be more details on some of the endpoints. We're still finalizing the presentation, but there absolutely will be additional details.

[Operator Instructions] The next question comes from the line of Ritu Baral of TD Cowen.

This is Joshua Fleishman on the line for Ritu. Curious, how do you believe ST-503's efficacy in Nav1.7 will compare to the recent small molecule Nav1.8 inhibitors? And have recent trial outcomes in Nav1.8 changed your conviction in Nav1.7 as a target?

So thank you very much for your question, and we've spent a lot of time looking at that data and discussing it and landed that we are even more convinced that NaV1.7 was the right target for us to go for. As you will -- as I think we've discussed before, because we are using a genomic way to target it and target the specific regulatory sequences of that gene, we could have gone for Nav1.8 or Nav1.7. And our belief was that the Nav1.7 control of the action potential that controls the pain signal was a more fundamental control. And one of the real pieces of evidence for that is that there are people out there that have got spontaneous mutations of Nav1.7 that just don't feel any pain. And there -- where it is very rare incidence is reported of Nav1.8 mutations, and they don't seem to have complete suppression of pain. So perhaps it isn't so surprising that the 1.8 results reported by Vertex were not as efficacious as had been hoped. So we are at the stage now of activating the study and hopefully, we'll have identified and recruited a patient soon. And we look forward to this. It's a dose-range finding study. And in our mouse studies, we see evidence of a dose-range response even in individual groups of mice. And we look forward to showing the suppression of pain because it's a really important unmet medical need. Great credit to Lilly and Vertex and others who are now pushing forward with non-opioid pain relief, but we believe Nav1.7 is the right target to go for.

The next question comes from the line of Yanan

This is Kuan-Hung for Yanan. So our question is also around Fabry. We are wondering, have you done any survey to either patients or physicians to understand that with the current product profile, what could be the potential adoption rate?

Can you just repeat that question again, please?

Sure. We are wondering, have you done any survey to either physicians or patients to understand that with the current product profile, what could be the potential adoption rate?

Nathalie, you spent a lot of time with the patient support groups. What's your thoughts on this?

Yes. So from the patient advocacy group, they are waiting for a better solution for a long time. The current standard of care is burdensome, but -- and there is some small improvement in their disease, but it really does not address all the symptom of the disease. It's a biweekly infusion that lasts many hours, which really impact their daily life. What we showed in our top line results for our patients that we have really improvement in the quality of life. It's a onetime injection and patients are uniformly saying this is what they're waiting for, for a long time. So they're really eager to see this drug approved. Some of the patients, because it's a genetic condition, want their family to have access to the product as soon as possible. So we have an overwhelming response from the patient community. Our PI, our principal investigators that are taking care of those patients are also extremely enthusiastic. When they're reviewing the data, they're really very impressed by what we've accomplished. So we do believe that the adoption rate, both from the patient side and the doc side will be very impressive.

And Nathalie, you met with cardiac experts recently, and they were very impressed.

Yes. We've met with cardiac experts to review our top line data with all the cardiac endpoints I mentioned. And first of all, they mentioned that we had many, many measures in the cardiac function that other study didn't have that was the most comprehensive set of data, and they were also very impressed with the data and the stabilization of the cardiac function. So we're focusing for the primary basis of approval on the eGFR slope and the renal function, but this is also a very important aspect of Fabry disease.

And the thing that -- when we go to these conferences, we often have Fabry patients come to us and tell us that they have received our treatment and how much their life has changed. And that kind of conversation spreads throughout the Fabry support groups and populations that we feel there's a real energy and anticipation. And then the final thing I would say, as you look at the 17 patients who came in on ERT who have remained off of ERT, and that's over 1,000 infusions, and they feel better. And the SF-36 scores say that they are better on this treatment. And so I really look forward to solving the commercial partner and getting this medicine to patients as soon as possible.

And I don't know if you can comment on this, but with the potential partners, do they share the same view? Or are they looking for something else, beyond what you have shared with the public?

So uniformly, all of the partners have -- all the potential partners have said how excited they are of the data. They are completely convinced that this is a medicine that is both safe and shows an effectiveness and a benefit to patients. I don't think -- I am sure you like us are aware of the environment for gene therapy at the moment in the United States and the stability that we all hope for and look for from the agency. Sangamo has had great interactions with the agency and continues to have them. And the partners just want to know that this is a stable place where their medicine will be well appreciated and taken forward. There is a second piece that makes the Sangamo discussions a little unusual and that since we got accelerated approval last year, we have compressed the activities that take you to the BLA submission into a very short time, which means that there are lots of interactions and lots of data points and new information coming where partners who will have in the past been interested in seeing the top line data have wanted to know that we have, as we do have agreement on the CMC. So we feel that this product is increasingly derisked. And now for the partners, that gives them comfort to be able to move ahead. And we -- I'm very pleased with the pace of negotiations at the moment and look forward to finding a positive way through this.

[Operator Instructions] The next question comes from the line of Gena Wang of Barclays.

This is Tony on for Gena. I guess just questions on upcoming updates in September. What data points should we be looking for, for the pain program in terms of how they would compare to existing NAV programs? And then also what incremental color should we expect for the Fabry update?

So the data that we'll be presenting at the conference in Berlin is preclinical data, and we will share more information about our GLP tox study in NHP and there will be also all the information on the mouse data and the non-GLP tox study. But the additional GLP showing the safety and efficacy of the product will be presented.

The next question comes from the line of Luis Santos of H.C. Wainwright.

My question is mostly regarding your cash runway and cash burn associated with -- especially associated with the initiation of the STAND trial where you plan to continue activating more sites and dosing the first patient by the end of the year. How is that going to weigh on your cash burn? And also, do you have any updates on your MINT platform? Any recent additional data or coming?

Louis, this is Prathyusha. I'll take the first one. So our intention is to continue taking the Nav1.7 program forward and dose patients as intended. As Sandy mentioned, our #1 priority is finding a Fabry commercialization partner, and that will help us solve for our funding needs in both in the long term and the short term. And maybe let me turn it over to Greg to answer the question on the MINT platform.

Yes. Thanks, Louis. We were happy to show the updates on the MINT platform at ASGCT recently. You probably saw lots of data there in relation to integration and -- or improvements in integration rates in primary cell types. So we're happy to share that data this year, and we continue to show that data to interested parties and engage in discussions with parties interested in collaborating with us.

And we have a number of ongoing discussions on the MINT platform.

And going back to the STAND trial, you said that you might have data by the end of next year. What kind of data should we expect?

So you can expect safety data from the patient and early efficacy data for the dose escalation trial.

And Louis, just -- you can be sure we're doing all the standard pain study scores, sleep assessment scores, even suicidality scores because these are patients whose life is dominated and tragically dominated by this. We will be -- sorry, it would be a 12-week endpoint that we would be showing by the end of next year, but we'll be following them long term because we think the huge advantage of Nav1.7 as a genomic medicine is a long-term benefit that will bring to the patients.

Yes. We expect to see a reduction.

Go ahead.

No, no, sorry, go ahead, please.

I was just going to say thank you for the added color. But if you have more color, always welcome.

No, I think Sandy mentioned it. So we're good.

I am showing no further questions at this time. I would now like to turn the call back to Louise Wilkie for closing remarks.

Thank you once again for joining us today and for your questions. As a reminder, you can access our presentation on the Investor Relations section of the Sangamo website. We look forward to keeping you updated on our future developments.

Thank you for your participation in today's conference. This does conclude the conference. You may now disconnect.

Thank you. We appreciate your help, Felicia.