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 timelines 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 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, which means we are on track to generate clinical data for this program anticipated toward 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 remains generally stable following the withdrawal of enzyme replacement therapy or ERT. We are excited to share for the first time a stabilization in cardiac endpoints, 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 biomarkers such as troponin and NT-proBNP, have remained stable in all patients at one-year follow-up. These data are striking, particularly given that cardiac function in Fabry patients tends to decline over time and is the leading cause of death in Fabry disease. Patients demonstrated a range of other clinical benefits, 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 was 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 demonstrates the potential for a single dose of ST-920 to treat the underlying pathology of Fabry disease and provide meaningful clinical benefit above the 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 of pain medication usage and the resumption of sweating, which has enabled these patients to perform physical tasks and exercise that they were previously unable to do. Following dosing with ST-920, all patients who came into the study on ERT were able to safely withdraw from ERT, with one patient now off ERT for more than 3 years. In doing so, this patient has already avoided more than 1,000 biweekly ERT infusions, 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 levels 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 the benefits of ST-920 over and above what they were experiencing with ERT alone. All 32 patients have transitioned into 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 toward 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 primates with no off-target effects observed. 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 patients. 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 models, supporting the potential of ST-506 as a one-time therapeutic approach for prion disease. We have completed a 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. 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. 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-2026. 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 2025. 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.

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. Let me clarify that we had a meeting last year with the FDA where they agreed on accelerated approval. At that meeting, they indicated that we could achieve accelerated approval with 1-year eGFR data and mentioned that we might want to submit 2-year data when it becomes available. Currently, we have 32 patients with 1-year data and 19 patients with 2-year data, and these two data sets are very similar and complementary. We have not yet held our pre-BLA meeting because it isn't the right time, but we are prepared for when and how to do that. The pre-BLA meeting serves as an operational discussion where we align with the agency on fulfilling the BLA requirements, including what sections need to be presented. We do not expect the agency to require anything beyond the 1-year data for accelerated approval. We anticipate providing them with yearly updates as these patients progress. Additionally, the earliest patient is now 4.5 years out, and the data appears very consistent and stable.

Got it. And then just another one. For the upcoming presentation at 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?

I will pass this on to Nathalie. However, I want to note that it would be quite unusual to dissect and show data for each individual patient in a dataset of 32 patients comparing them before and after treatment. Therefore, we do not plan to present that at the meeting in Japan. We might include it in a larger publication we are currently working on. 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 on 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.

The next question comes from 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?

Thank you for your question. We've spent considerable time analyzing the data and discussing it, and we are even more convinced that targeting NaV1.7 is the right choice for us. As we've mentioned previously, since we are using a genomic approach to focus on specific regulatory sequences of that gene, we could have chosen either Nav1.8 or Nav1.7. However, we believe that Nav1.7 plays a more fundamental role in controlling the action potential related to pain signaling. There is concrete evidence of this: some individuals with spontaneous mutations in Nav1.7 do not feel any pain, whereas cases of Nav1.8 mutations are very rare and do not result in complete pain suppression. Therefore, it may not be surprising that Vertex's results with Nav1.8 were not as effective as anticipated. We are currently activating the study and hope to identify and recruit patients soon. This is a dose-range finding study, and our mouse studies indicate a dose-response relationship even within individual groups. We are eager to demonstrate pain suppression, as this addresses a significant unmet medical need. We commend Lilly, Vertex, and others for advancing non-opioid pain relief, but we remain confident that Nav1.7 is the appropriate target.

The next question comes from the line of Yanan Zhu of Wells Fargo.

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?

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 there is some small improvement in their disease, but it really does not address all the symptoms of the disease. It's a biweekly infusion that lasts many hours, which really impacts their daily life. What we showed in our top line results for our patients is that we have a really improvement in the quality of life. It's a one-time 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 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. We do believe that the adoption rate, both from the patient side and the doctor 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. First of all, they mentioned that we had many, many measures in cardiac function that other studies didn't have, which was the most comprehensive set of data, and they were also very impressed with the data and the stabilization of 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.

When we attend these conferences, Fabry patients often approach us to share how our treatment has significantly improved their lives. These conversations resonate within the Fabry support groups, generating real excitement and expectation. Additionally, I want to highlight that 17 patients who transitioned from ERT have successfully remained off it, totaling over 1,000 infusions, and they report feeling better. The SF-36 scores indicate their improvement with this treatment. I am eager to resolve the commercial partnership situation and make this medicine available to patients as quickly 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?

All the potential partners have expressed their excitement about the data. They are fully convinced that this medicine is both safe and effective with benefits for patients. I believe you are aware of the current environment for gene therapy in the United States and the stability we all hope to see from the agency. Sangamo has had positive interactions with the agency and continues those discussions. The partners want assurance that this is a stable environment where their medicine will be embraced and advanced. Additionally, since we received accelerated approval last year, we have expedited the activities leading to the BLA submission, resulting in numerous interactions and data points. Partners who might have been interested in seeing the top line data are assured that we have agreement on the CMC. We feel that this product is increasingly derisked, which provides comfort for the partners to move forward. I am very pleased with the current pace of negotiations and look forward to finding a positive resolution.

The next question comes from 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. Additionally, the 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, particularly in relation to the initiation of the STAND trial, where you plan to activate more sites and dose the first patient by the end of the year. How will this impact your cash burn? Additionally, do you have any updates on your MINT platform? Any recent data or upcoming information?

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 number one priority is finding a Fabry commercialization partner, and that will help us solve our funding needs in both the long term and the short term. 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 improvements in integration rates in primary cell types. We are 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, you can be sure we're conducting all the standard pain study scores, sleep assessment scores, and even suicidality scores because these patients’ lives are unfortunately dominated by this condition. We will be showing a 12-week endpoint by the end of next year, but we will also follow them long term because we believe that the significant advantage of Nav1.7 as a genomic medicine is the long-term benefit it will provide to the patients.

Yes. We expect to see a reduction.

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.

Thank you, Felicia.