Sangamo Therapeutics, Inc.

Good afternoon, and welcome to the Sangamo Therapeutics fourth quarter and full year 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 McRae, Chief Executive Officer, Natalie Dubois-Stringfellow, Chief Development Officer, Nikunj Jain, Interim Chief Financial Officer, and Greg Davis, Head of Research and Technology. 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 related 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 fibroid disease programme, the anticipated plans of Sangamo and its collaborators for clinical trials, regulatory submissions and regulatory approvals, and other statements that are not historical fact. Actual results may differ materially from what we discussed today. These statements are subject to certain risks and uncertainties as are discussed in our filings of the SEC, specifically in our annual report on Form 10K for the fiscal year ended December 31, 2025, and subsequent filings and reports that Sangoma makes from time to time with the SEC. The forward-looking statements today are, 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 McRae.

Thank you, Louise, and good afternoon to everyone joining the call today. Sangam will continue to make significant pipeline progress in 2025 and into the first quarter of 26. Set against a backdrop of regulatory and market uncertainty and with limited cash resources, In June, we announced positive top-line results from the Registrational STAR study in Fabry disease, including a positive mean annualized estimated glomerular filtration rate, or EGFR, slope at 52 weeks across all dose patients in the study, which, as the US FDA reiterated in October 2025, may serve as the primary basis of approval under an accelerated approval pathway. The rolling submission of a biologics license agreement, or BLA, to the FDA is in progress, seeking ST920 approval, Sangamo's first ever wholly owned BLA submission. We transitioned to become a clinical stage neurology company with six clinical sites activated in the Phase 1-2 STAMP study in chronic neuropathic pain. In April, we continue to demonstrate that we're a collaborator of choice for neurotropic capsids with the announcements of a third neurology capsid license agreement, this time with Eli Lilly, to deliver genomic medicines for up to five central nervous system disease targets. And we have raised over $130 million in funding since the start of 2025 through non-dilutive license fees and milestone payments, as well as equity financing. These are important achievements, and I would like to sincerely thank everyone at Saigon for their hard work, dedication, and continued focus on our mission to help patients in need. I would now like to hand directly over to Natalie Dubois-Stringfell, our Chief Development Officer, to provide recent business updates from our prioritised pipeline. I will then close the call by summarising the key broader business takeaways from this quarter. Natalie.

Thank you, Sandy. First, I am pleased to share updates from our Registrational Phase 1-2 STAR study evaluating isoragal gene Sivaparvovac, or ST920, our investigational gene therapy for the treatment of adults with Fabry disease. In December, we were happy to initiate the rolling submission of a BLA to the U.S. FDA seeking approval of ST920 under an accelerated approval pathway. Rolling submission allows for completed module of the BLA to be submitted and reviewed by the FDA on an ongoing basis rather than waiting for the entire BLA to be submitted at once. We have now submitted both the non-clinical and the clinical modules to the FDA. In addition, the antibody assay companion diagnostic, which is designed to screen patients for eligibility with ST920, has been submitted to and accepted by the FDA Center for Devices and Radiological Health, or CDRH, seeking pre-market approval. These are significant milestones for Sangamo and for Fabry Patient in Need. I would like to sincerely thank everyone at Sangamo involved for their significant efforts in getting us to this point. The next key milestone is completion of the Chemistry, Manufacturing, and Controls, or CMC, module. We are very pleased to have completed manufacturing and testing of the process validation lots with acceptable results achieved and to have completed method validation. We are also excited to have manufactured our first commercial lot. We are working hard to advance the remaining required activities and anticipate completing submission of the BLA as early as this summer, subject to our ability to secure adequate additional funding. In February, we presented detailed clinical data via four platform and poster presentation in the 22nd Annual Word Symposium that took place in San Diego, California. We believe this encouraging data continue to demonstrate the potential for the endogenous production of Alpha-GalA activity following ST920 administration to transform the Fabry treatment landscape. With a positive mean annualized EGFR slope at one year across all those patients in the study and at two years for 19 patients, we continue to see improved kidney function, which marks a notable departure from the historical renal decline characteristic of the disease. The stabilization in cardiac function, including stability of cardiac structure and cardiac biomarkers, is also especially encouraging. given that cardiovascular disease is the most common cause of death in Fabry disease patients. And we were pleased to give a platform presentation dedicated entirely to this important topic, showcasing new cardiac-specific data. In addition to a well-tolerated safety profile, the ability to withdraw from enzyme replacement therapy and a range of other clinical benefits This data continues to demonstrate how ST920 shows potential as a one-time durable treatment option for Fabry disease that could fundamentally shift the current treatment paradigm. At World, we also presented platform presentation on pharmacology and immunogenicity outcomes from the STAR study alongside a fertility, embryo fetal development, AAV integration, and germline transmission risk study in mice. All four presentations are available on the Sangamo website. Next, I'd like to focus on our prioritized neurology pipeline. As in December, we were thrilled to receive fast track designation for SC503, our investigational epigenetic regulator for Fabry with, for patients, sorry, with intractable pain due to small fiber neuropathy or SFN. As a reminder, Fast-track designation aims to facilitate the development and expedite the review of new therapeutics that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Companies granted this designation are given the opportunity for more frequent interaction with the FDA. This clinical program may also be eligible to apply for accelerated approval and priority review if relevant criteria are met. SFN is a debilitating chronic pain disorder with limited effective current treatment options. So this designation underscores the high unmet patient need in SFN and the urgency to develop safe and effective non-opioid treatment alternatives. Since the last update, We have activated an additional four clinical sites in the Phase I-II Stent Study evaluating SC503 to achieve a total of six active sites. These sites are working on identifying patients. Last week, we were also pleased to have a manuscript published in Science Translational Medicine detailing the preclinical safety and pharmacology of SC503 in human neurons, mice, and non-human primates. These promising results provide the preclinical foundation for our Phase I-II STANS study. Finally, moving to ST506, 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. The good laboratory practice or GLP toxicology study has been completed and analysis is ongoing. I would like to hand back to Sandy to provide a broader business and financial update. Sandy?

Thank you, Natalie. In closing, in times of regulatory change and careful financial management, we are pleased with the pipeline progress we have made since the start of 2025. A positive top-line readout in our Fabry Disease Program alongside continued productive engagement with the FDA have resulted in a rolling submission of the BLA for ST920 with the first two modules submitted. We became a clinical stage neurology company with the initiation of the Phase 1-2 STAN study in SFN, and we received fast-track designation from the FDA for this program. And we have continued to show Sangamo as a collaborator of choice for neurotropic capsids with announcements of our third STAC BDB license agreement. These are important advancements. However, we will not be satisfied until we solve our long-term cash runway. Securing a commercial partner for Fabry remains our number one focus, and we continue to engage in Fabry business development discussions with multiple potential partners. Like me, I know many of you feel frustrated that this process is taking so long. Discussions of this nature are complex, and facilitating the extensive due diligence required by potential partners takes time, as they assess the regulatory environment for gene therapies. We also continue to seek ways to raise additional capital, including an assessment of all strategic options for each of our assets. and are in discussions with multiple potential partners, including alongside our focused efforts to secure a fabric commercialization partner. We will share more information as soon as we are able. Operator, please open the line for questions.

To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from Maury Raycroft with Jefferies. Your line is open.

Hi, this is James on for Maury. Thanks for taking our questions. Just to start off, can you provide more color on the revised timing for the FABRI BLA submission? What PPQ and other CMC-related activities are the primary gaining factors here? And separately, I know you just touched on this, Sandy, but can you comment on the status of the FABRI partnership discussions, whether the same counterparties previously engaged remain in dialogue with Sangamo, and whether recent leadership changes at CBIR have had any impact on those discussions? Thanks.

Thank you, Morrie. That's an important set of questions. So when we were given guidance that we could file for accelerated approval with a single study, the clinical data timelines were very clear because the patients were already in the study. We then had to hustle to complete the CMC activity that would normally be performed over phase two and phase three. And so the CMC has always been the piece that has been on the critical path for our filing. We've also had a number of very, very helpful interactions with the CMC group at the FDA. Most recently, they've given us very clear, detailed pages of guidance on what was needed to complete the submission and maximize its chance of success. And, of course, we are following those to the letter and making sure that we do all the right things for CMC, which is often the piece that is most challenging for cell and gene therapies. And then there's a third bit that we haven't spoken about as much, which is we are managing our cash very carefully. We're managing our spending, and we want to ensure that our runway gives us the best possible time to fulfill a fabric partnership. That wise, prudent spending combined with the agency's requirement has just led to the timeline for the CMC being a little longer than it previously was. You asked about the partnerships. We have been talking to people for 18 months, a variety of people. Most of the ones we spoke to last year have now gone and many of the times it was because of regulatory uncertainty. We are now speaking to multiple partners and are having good conversations with them. But these three are new to the discussions, and so we need to go through the process of deep diligence, management presentations, and then negotiations. Maury, trust me, the team are doing everything possible to find the right partner and get this to patients when we are so close to a filing of a medicine that is going to fundamentally change the way fabric patients are treated.

Thank you so much.

Thank you. As a reminder, to ask a question, please press star 11 on your telephone. Again, that is star 11 to ask a question. Our next question comes from Patrick Trucchio with HC Wainwright. Your line is open.

Hi, everyone. This is Luis Santos in for Patrick. Thank you for taking our questions. I was wondering if you have had any additional interactions with the FDA recently or have any additional FDA interactions planned, specifically relating to the acceptance of the EGFR slope as a primary endpoint, and if anything has changed given the recent FDA changes. Thanks so much.

Thank you, Luis. So, we spoke to the agency last October of last year and feel that they reiterated that the EGFR at one year could be used to file for accelerated approval. We haven't gone back to them. It's always a question of fulfilling what they've asked and submitting it. And we're now halfway through the rolling submission. We've submitted the clinical module and the preclinical module. We've submitted the companion diagnostic. The The CMC is in process, and then there's a final piece that kind of pulls it all together and gives the full summary. So we don't plan to go to the agency again because we're already partway through the process. If the agency changes or their way of dealing with gene therapy changes, we would, of course, address that. But at the moment, we feel we have enough guidance to move ahead.

Thank you so much for the detail. Appreciate it.

Thank you. Thank you. I'm showing no further questions at this time. Oh, we do have a question from Luca Issi. Your line is open.

Thanks for taking our question. Thanks, team. This is Cassie for Luca. On prime disease, maybe quickly, you mentioned that this is your first in-human trial for STAC-DBB capsid. Does that timeline also account for your partnered programs that DBB's clinical proof of concept will be the prime one will be the first trial? and your partner's entrance into clinic or behind that. And related to it, when we look at which programs has the STAC-BVD-TABSIT, is there an aspect of the approach that makes it more suitable for some indication versus others, or the decision to use the intracerebral AV9 for neuropathic pain, for example, is just a matter of timing? Thanks so much.

So I'm not sure I... Understood. I heard all the parts of that, but let me try and answer what I think you were asking. I think you asked, why did we use AV9 for neuropathic pain? And that program was started four or five years ago before the STAC-BVB capsid was known. And AV9 is very effective when given intrathecally at dosing the dorsal root ganglion. So it would be the logical choice. And AV9 has been used and been seen to be safe and effective. Our STAC BBB, we're very pleased and we're very pleased to have such eminent neurological companies choosing STAC BBB and taking it forward. They are fortunate to have um great resources and we are working with each one of them to help them to understand the capsid and take it forward and we're we feel we have good relationships with all of the three and we're encouraged by their enthusiasm to move their programs forward

Thank you. And I'm 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 Sangamore website. We look forward to keeping you updated on our future developments.

This concludes today's conference call. Thank you for participating. You may now disconnect.