Good morning, and welcome to Sangamo Therapeutics Third Quarter 2025 Conference 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 morning, 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; Greg Davis, Head of Research and Technology; Prathyusha Duraibabu, Principal Financial Officer and Principal Accounting 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 September 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 morning to everyone joining the call today. This quarter, we continue to advance our clinical and preclinical pipeline while managing our cash resources carefully. In September, we presented promising detailed clinical data from our registrational STAAR study in Fabry disease, demonstrating the potential for ST-920 as a one-time durable treatment of the underlying pathology of Fabry disease for all types of Fabry disease patients. And in October, we were pleased to hold a meeting with the FDA to discuss the proposed efficacy and safety data package for a planned BLA submission where in the meeting minutes, the FDA reaffirmed its October 2024 agreement to use eGFR slope as an endpoint to support an accelerated approval pathway. A particular highlight for me this quarter was attending the 15th Annual Fabry Family Education Conference that brought together more than 200 Fabry patients, family members, and volunteers to provide educational presentations and gather insights from patients, including those who have received ST-920. This is an event we are privileged to attend each year, and it was humbling to spend time with this group of inspirational people of all age groups to learn more about their experiences with Fabry disease. I found it striking to hear firsthand the challenges these patients face, including their experiences with currently available treatments, yet also see the hope they have for treatment breakthroughs and their strong understanding of scientific advances and their unwavering support for one another. I came away from the event more convinced than ever that patients are seeking an alternative to current standards of care alongside the peaks and troughs and associated symptoms that they can bring. Gene therapy, where the alpha-Gal A enzyme is expressed all day, every day by the liver, is a fundamentally different treatment modality to what is available today. I was lucky to meet with some patients who received ST-920 as part of the STAAR study, and their enthusiasm and excitement was overwhelming. They couldn't wait to tell me their experiences, and one patient approached me to share how ST-920 has completely transformed their life. We have a responsibility to bring this medicine to the Fabry community. In our prioritized neurology pipeline, we are excited now to be recruiting and enrolling patients in the Phase I/II STAND study in chronic neuropathic pain, our first-ever neurology clinical study following the activation of the first two clinical sites. We also continue to advance our prion program ahead of the planned CTA submission next year. I would like to now hand directly over to Nathalie Dubois-Stringfellow, our Chief Development Officer, to provide additional details on these important programs. Prathyusha Duraibabu, our Principal Financial Officer, and I will then close the call by summarizing the key business and financial takeaways from this quarter.

Thank you, Sandy. First, I am pleased to share updates from our registrational Phase I/II STAAR study evaluating isaralgagene civaparvovec or ST-920, our investigational gene therapy for the treatment of adults with Fabry disease. This quarter, we presented encouraging detailed clinical data at the ICIEM 2025 Conference in Kyoto, Japan. As we have shared previously, after 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 patients dosed in this study. Furthermore, a positive mean annualized eGFR slope of 1.7 was observed in the 19 patients who have achieved 2 years of follow-up. Supportive mean annualized eGFR slopes were also observed across a variety of patient subgroups, including gender, baseline ERT status, Fabry disease type, and baseline eGFR, showing consistency in effect across Fabry patients in the study. For the first time, we share cardiac data, including stable cardiac morphology, stable cardiac function, and stability in early markers of cardiac damage in the 32 patients with at least 52 weeks of follow-up. These data are encouraging, particularly given that cardiac disease is a leading cause of death in Fabry disease patients. As we have outlined previously, a range of key secondary endpoints were also positive. We continue to see strong durability in the study, up to 4.5 years for the longest treated patient, and we are pleased to see an encouraging ongoing safety profile. Indeed, every day that passes, we accumulate more data. And as of today, we are pleased to have 3 patients with at least 4.5 years of follow-up. We believe that these data demonstrate the potential of ST-920 to provide meaningful and long-lasting clinical benefit to a wide range of Fabry disease patients, even above current standard of care. In October, we held a meeting with the FDA to discuss the proposed efficacy and safety data package ahead of the planned BLA submission. We are pleased that the FDA meeting minutes reiterated the October 2024 agreement that we may use eGFR slope as an endpoint to support an accelerated approval pathway, agree on the adequacy of the safety package to support the BLA submission, and provided valuable input on the clinical data package. We continue to prepare for our anticipated BLA submission under the accelerated approval pathway planned for as early as the first quarter of 2026. Next, I'd like to focus on our prioritized neurology pipeline, as this quarter, we've commenced patient enrollment and recruitment in the Phase I/II STAND study evaluating ST-503, our investigational epigenetic regulator for patients with intractable pain due to small fiber neuropathy or SFN, following the activation of our first two clinical sites. SFN is a truly debilitating chronic neuropathic pain impacting more than 650,000 people across the U.S., Europe, and Japan. We are thrilled to be recruiting patients for our first-ever neurology genomic medicine clinical study and expect to dose the first patient in the coming months. This quarter, we are also pleased to present updated nonclinical data at the 9th International Congress on Neuropathic Pain in Berlin, Germany, which demonstrated the durability, potency, and selectivity of ST-503 in nonhuman primates alongside a favorable safety profile. We believe the preclinical data for this program is compelling, and we look forward to seeing how this translates into humans. We believe chronic pain is an area of strong market potential, and we're particularly encouraged by the FDA's recent draft guidance on the development of non-opioid analgesics for chronic pain, which seeks to accelerate safe and effective non-opioid treatment and to reduce prescription-related opioid misuse. We stand with the FDA in seeking safe, effective alternative pain relief options. As a reminder, this is a dose escalation study, which, if positive, could allow us to broaden into other potentially high-value indications such as trigeminal neuralgia or oncology-related chronic pain. Nav1.7 is a well-proven target with human genetic validation, which we believe provides pain franchise potential. Finally, moving to ST-506, our epigenetic regulator for the treatment of prion disease to be delivered intravenously using our neurotropic STAC-BBB capsid. This quarter, we continue to advance clinical trial application or CTA-enabling activities for the program, ahead of our expected CTA submission as early as mid-2026. Following on from our productive meeting with the U.K.'s MHRA earlier this year, where we aligned on nonclinical safety and the clinical study design, this quarter, we were pleased to hold another productive interaction with the MHRA, this time to align on the planned chemistry, manufacturing and controls, CMC strategy for the anticipated CTA submission. In November, we presented updated preclinical data at the Prion 2025 Conference, which demonstrated the potent combination of epigenetic regulator and capsid delivery technology for the treatment of prion disease, including a profound survival extension that was observed in an aggressive mouse model of prion disease alongside widespread brain delivery and significant prion reduction in nonhuman primates. Based on this compelling preclinical data, we are preparing for the CTA submission to test 506 in the clinic. Given the rapidly deadly nature of prion disease with no currently available treatment option, we anticipate demand for this planned study to be high with a short time frame to an expected data readout. Furthermore, this study would mark the first-in-human testing of our STAC-BBB capsid, which, if successful, could unlock a broader neurology pipeline for advancement, including with potential partners. We have deliberately chosen 2 lead neurology assets that use different delivery mechanisms and bring different development risks. We believe both of them independently offer significant potential value and provide additional expansion opportunity into related neurological indications.

Thank you, Nathalie. This quarter, we continue to diligently prioritize and control spend while seeking ways to extend our cash runway as we continued business development discussions for a Fabry commercialization agreement. In October, we received $6 million upon Pfizer's exercise of a buyout option from our 2008 license to use zinc finger modified cell lines. We also continue to engage in business development discussions across our Sangamo pipeline and platforms. As of today, we believe our cash and cash equivalents, including the license fee received from Pfizer and proceeds from sales of common stock under our at-the-market offering program since September 30 will be sufficient to fund our planned operations into the first quarter of 2026. Before handing back to Sandy, I'd like to emphasize that we remain resolutely focused on solving our long-term funding foundation to advance our promising medicine pipeline. In the near term, we seek to bridge to that future through a balanced approach, actively pursuing non-dilutive business development opportunities while exploring appropriate capital options. I will now hand it back to Sandy for closing remarks.

Thank you, Prathyusha. To close, I'm pleased with the pipeline advances this quarter. We held a meeting with the FDA where in the meeting minutes, the FDA reiterated its October 2024 guidance that we may use eGFR slope as an endpoint to support an accelerated approval pathway. We presented detailed data from our registrational STAAR study in Fabry disease, including a positive mean annualized eGFR slope at 52 weeks, and we're pleased to observe a wide range of other positive secondary endpoints. Taken together, we believe in the potential for ST-920 to provide meaningful, multi-organ, clinical benefits above current standards of care. The importance of this data has also been recognized externally with the acceptance this week of 3 platform presentations on our Fabry disease program at the upcoming WORLDSymposium in 2026. This quarter, we began recruiting and enrolling patients in the Phase I/II STAND study for chronic neuropathic pain following the activation of the first 2 clinical sites. We expect to dose the first patient in the coming months. And we continue to advance our prion program towards an anticipated CTA submission as early as mid-2026. As Prathyusha outlined, solving our long-term funding needs remains our #1 priority. We continue to seek ways to raise additional capital alongside our focused effort to secure a Fabry commercialization partner. Before closing for questions, I want to reflect on the recent Nobel Prize in Physiology or Medicine awarded to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their research on regulatory T cells or Tregs. At Sangamo, we proudly advanced the clinical development of Tregs being the first known company to dose a patient with an engineered CAR-Treg. In August of this year, we presented the clinical data from our TX200 study in kidney transplantation at the World Transplant Congress in San Francisco, showing the clinical potential of CAR-Tregs to create a tolerogenic environment in the kidney, alongside the ability to taper immunosuppression post TX200 dosing. These are encouraging results that we believe demonstrate the potential for engineered CAR-Tregs in organ transplantation. And we really want to say that we are thankful to everyone who has been involved in this first-in-human study. While we are pleased with these innovative scientific advances, we remain focused on our promising neurology pipeline and look forward to sharing further novel scientific developments with you all. Operator, please open the line for questions.

Our next question comes from Gena Wang from Barclays.

This is Hang Hu from Barclays on behalf of Gena Wang. Just a couple of questions on Fabry disease. Could you share with us what's the latest progress in your partnership deal negotiation? And also on the regulatory front, you shared your progress with the FDA. But in light of recent news from CBER about uniQure, is there any read-through to your Fabry disease drug program?

So I can't comment on the discussions uniQure had. What they're doing is important and difficult, and we simply wish them well for patients with Huntington's disease. But what I can tell you about is our interactions with the agency and the written meeting minutes that we have that confirm our ability to use the eGFR data for one year to get accelerated approval. And when we look at our data, the eGFR is very clear and compelling, but it's the overall body of data, the safety of the product, the ease of use, the cardiac data, the SF-36, the kidney benefit. And I believe that's what the agency sees, and that's why they have remained steadfast in endorsing the use of eGFR at one year to allow us accelerated approval and to file this next year. We have also had other interactions with the agency on CMC and manufacturing. And I know those sometimes aren't quite as exciting as the clinical path forward. But for genomic medicines and for AAV manufacturing, having the agency's agreement on how you will manufacture it and what the packaging that is going to be required for approval is, is essential. And so we are very confident on that progress. And just to kind of reflect on that, now that the agency has reaffirmed our accelerated approval pathway, this can only be helpful for our business development discussions.

Yes. How about the first part of this question? Like could you share with us any progress and your status in partnership negotiation?

I'll just repeat what I said at the end there that now that the FDA has reaffirmed both the CMC and the clinical pathway, it can only be helpful in those discussions.

Our next question comes from Maury Raycroft from Jefferies.

I want to follow up on the last question. Are you planning to have any additional meetings with the FDA before the pre-BLA meeting? Do you intend to have a pre-BLA meeting, and what further clarification do you require from the FDA at this stage?

Nathalie, can you answer that?

Yes, we are very pleased with the clarity we received from the FDA regarding the clinical and safety package required for the BLA submission. Additionally, we have a clear understanding of the components needed for the CMC strategy. This interaction was recent, and we are currently considering whether there are any other topics that may warrant a pre-BLA meeting.

Nathalie, this is a bit of a regulatory fine point. One doesn't have to have a pre-BLA meeting if you feel all the questions have been answered.

Absolutely. And because we have RMAT, we've had this year many interactions, either through meetings or correspondence where we had really good clarity on many of our questions. So at this point, we're really discussing internally if there is anything that remains to be discussed. But there is the pre-BLA...

The RMAT process works well, doesn't it, because it allows that ongoing interaction.

Exactly. Exactly. Yes, we were very pleased this year on the responses from the FDA, and they were always on time, and we've had no delays in our discussions.

Got it. That's helpful. For the BD partners, assuming that this is a three-way conversation where you're sharing the regulatory information with them, do you need any further clarity on the regulatory aspects that the BD partners require to make a decision?

I don't think there are any remaining questions. We have a clear understanding of the primary endpoint, and the agency has reviewed our one-year data. This was part of the reason for our recent clinical meeting. Previously, we presented data on 18 patients at one year, and now we have data on 32 patients at one year and 19 patients at two years, with consistent eGFR slope results. This is crucial information that potential partners would want to know. Additionally, the CMC and manufacturing pathways are clear, and the manufacturing process is already in motion.

Our next question comes from Wells Fargo.

This is Kuan-Hung for Yanan. So our question is also around the Fabry program. Can you share with us in your engagement with the FDA, has the topic of Commissioner's National Priority Review Voucher ever been mentioned? And do you think that could affect your BD discussions?

Yes. No, we have not discussed specifically that, but we are looking into it.

Got it. And have you shared all the details regarding the FDA meeting minutes with your potential partners? And any color you can comment on their reactions?

When we received the minutes, we were glad to share them with our partners or convey their essence. Any partnership that progresses will definitely involve the partners reviewing the minutes as part of the process, ensuring they see all regulatory correspondence related to any business development deal.

Our next question comes from Patrick Trucchio from H.C. Wainwright.

This is Luis Santos for Patrick. First, I want to say it is great to see the progress, and the extension of your runway is commendable and reflects your financial discipline, and we appreciate that. I want to ask a couple of questions about 503 in neuropathic pain and the STAND study regarding the dosing that will start in the coming months. Are there any additional challenges we should consider in recruiting this patient population? Also, looking ahead to the readout in about a year, what would be a clear win to move this program forward? I have a follow-up.

Nathalie, can you comment about how we're doing with getting the study going?

We are pleased to have already activated two sites that are currently screening patients and assessing the population. We have also expanded the population criteria to include SFN, not just idiopathic small fiber neuropathy, which increases our ability to find patients. We are very optimistic about dosing the first patient in the coming months. Additionally, we are actively working on opening more sites, aiming for up to ten in the study. Regarding the success of the trial, this is a dose escalation study focused on safety and tolerability, while we also assess efficacy based on pain reduction from baseline using the Pain Intensity Numerical Rating Scale, a widely recognized tool for measuring pain. We will be monitoring this in a blinded manner throughout the dose escalation phase.

Nathalie, it's been interesting the number of patients that have spontaneously from other places written to us and tried to get into the trial. It's clear that there's a high unmet medical need here.

Yes, absolutely. People have reached out to Sangamo or have seen the site activated in the clinicaltrial.gov page and have been directly contacting the site to see if they could be eligible throughout the country.

And regarding your platform, can you discuss any ongoing partner interest in the STAC-BBB capsid? Any additional deals that could extend your runway? And also with your MINT platform progressing?

We're pleased with the progress of the capsid and we are constantly engaging with new individuals about it. It is also essential to note that our partners working on the capsid, such as Genentech, Astellas, and Lilly, are satisfied and our relationship and discussions with them are progressing positively. Greg, how is MINT performing?

MINT is doing well. So we continue to advance that platform in ways where we have minimal spend. So we're trying to de-risk that technology from a molecular standpoint for MINT design towards genomic targets. And we're trying to use our money wisely in that to keep that moving forward. And we continue to advance business development negotiations for potential MINT partnership and look forward to sharing more information on those when we're able to.

The success of the integration with the MINT platform is increasing every time the team demonstrates it to me. It is a fundamentally important piece of science that we hope to discuss more in the future and ideally enable others and Sangamo to develop medicines from.

This does conclude the question-and-answer session. I would now like to turn it back to Louise Wilkie for closing remarks. The floor is yours.

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.

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