{"url_path":"/sec/sgmo/10-k/2026/item-1","section_key":"item-1","section_title":"Item 1 BUSINESS","topic":"sec","document":{"doc_type":"10-K","doc_date":"2026-03-30","source_url":"https://www.sec.gov/Archives/edgar/data/1001233/0001628280-26-022029-index.html","accession_number":"0001628280-26-022029","cik":"0001001233","ticker":"SGMO","issuer_name":"SANGAMO THERAPEUTICS, INC","edgar_url":"https://www.sec.gov/Archives/edgar/data/1001233/0001628280-26-022029-index.html","primary_entity_key":"0001001233","primary_entity_name":"SANGAMO THERAPEUTICS, INC"},"word_count":23228,"has_tables":true,"body_markdown":"ITEM 1 – BUSINESS\n\nOVERVIEW\n\nWe are a genomic medicine company committed to translating ground-breaking science into medicines that transform the lives of patients and families afflicted with serious neurological diseases. We believe our zinc finger epigenetic regulators are ideally suited to potentially address devastating neurology disorders and our capsid engineering platform has demonstrated the ability to expand delivery beyond currently available intrathecal delivery capsids, including in the central nervous system, or CNS, in preclinical studies.\n\nOur Core Neurology Programs\n\nOur neurology development is focused on two innovative areas: (i) development of epigenetic regulation therapies to treat serious neurological diseases and (ii) development of novel engineered adeno-associated virus, or AAV, capsids to deliver our therapies to the intended neurological targets.\n\nInitial indications for our wholly owned preclinical programs include small fiber neuropathy, or SFN, a type of chronic neuropathic pain, and prion disease. Following clearance in November 2024 of the investigational new drug application, or IND, from the U.S. Food and Drug Administration, or FDA, for ST-503 for the treatment of SFN, the first six Phase 1/2 clinical sites have been activated, and we have begun patient recruitment and enrollment. We have also begun to prepare a clinical trial application, or CTA, for our product candidate to treat prion disease.\n\nIn addition, we are party to collaboration and license arrangements pursuant to which our collaborators are developing preclinical product candidates in indications such as tauopathies, amyotrophic lateral sclerosis, or ALS, and other undisclosed neurology targets. These partners include Genentech, Inc., a member of the Roche Group, or Genentech, Astellas Gene Therapies, Inc., or Astellas, Alexion Pharmaceuticals, Inc., or Alexion, Eli Lilly and Company, or Lilly, and Takeda Pharmaceutical Company Limited, or Takeda.\n\nWe also are developing novel engineered AAV capsids enhanced for delivery to neurological targets and have identified a proprietary engineered neurotropic AAV capsid variant, STAC-BBB, that has demonstrated an ability to cross the blood-brain barrier, or BBB, in nonhuman primates, or NHPs, and in mice, and mediated robust transduction, transgene expression, and targeted epigenetic repression throughout the brain and spinal cord after intravenous, or IV, administration. We believe this novel capsid has the potential to unlock multiple wholly owned neurology epigenetic regulation programs, and is already the subject of multiple license agreements, including with Genentech, Astellas and Lilly.\n\nOther Clinical Programs\n\nOther clinical-stage product candidates include:\n\n•Isaralgagene civaparvovec, also known as ST-920, our wholly owned gene therapy product candidate for the treatment of Fabry disease, was evaluated in our completed registrational Phase 1/2 STAAR clinical study and continues to be evaluated in the subsequent long term follow up study. We believe this product candidate has a clear regulatory pathway to Accelerated Approval from the FDA. Rolling submission of the Biologics License Application, or BLA, for isaralgagene civaparvovec was initiated in December 2025.\n\n•Giroctocogene fitelparvovec, also known as SB-525, is a gene therapy product candidate for the treatment of moderately severe to severe hemophilia A, that we co-developed with, and licensed to Pfizer Inc., or Pfizer, and to which we regained development and commercialization rights in April 2025. We have completed the transition of the program back to Sangamo, and we currently are in business development negotiations with a potential collaboration partner for giroctocogene fitelparvovec.\n\nOur Novel Science and Technologies\n\nWe are a leader in the research and development of zinc finger proteins, or ZFPs, which are abundantly occurring human proteins that have evolved to regulate the genome through interactions with DNA and regulatory proteins. Our strategy is to translate our differentiated and versatile zinc finger, or ZF, technology platform to create product candidates with best- or first-in-class clinical potential. We believe that the versatility and flexibility of our technology platforms enable us to design therapeutic approaches to resolve the underlying genetic or cellular causes of disease, using whichever technology is best suited to deliver that treatment. Our current area of focus is developing epigenetic regulation therapies with our ZF technology platform for serious neurological diseases.\n\n7\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nWe are also evaluating several potential routes of administration for our neurology-targeted investigational therapies, as delivery of genomic medicines to the CNS is a significant obstacle to developing therapies treating neurological disorders. We have developed a proprietary AAV capsid engineering platform, Selecting In vivo For Transduction and Expression of RNA, or SIFTER, with the aim of engineering capsids with improved CNS transduction and have presented results from capsids for both IV and cerebrospinal fluid, or CSF, administration.\n\nWe are also developing next generation modular integrase technology, engineered to enable large-scale genome editing. Building on our deep expertise in protein-DNA interactions derived from our zinc finger platform, the Modular Integrase, or MINT, platform is a versatile, protein-guided genome editing method designed to integrate large sequences of DNA into the genome to potentially treat – with a single medicine – many different patients who have unique mutations in the same gene.\n\nIn the process of developing these technologies, we have additionally accrued significant scientific and development capabilities, as well as manufacturing know-how, that are broadly applicable to the field of gene therapy, which we have used to develop our genomic medicine product candidates.\n\nManufacturing\n\nWe expect to be substantially reliant on external partners to manufacture clinical supply for our neurology portfolio. We retain our in-house analytical and process development capabilities.\n\nCollaborations and Licenses\n\nOur collaborations with biopharmaceutical companies bring us important financial and strategic benefits and reinforce the potential of our research and development efforts, including our proprietary ZF technology and AAV capsid platforms. They leverage our collaborators’ therapeutic and clinical expertise and commercial resources with the goal of bringing our medicines more rapidly to patients. We believe these collaborations reflect the value of our technology and will potentially expand the addressable markets of our product candidates. To date, we have received approximately $911.0 million in upfront license fees, milestone payments and proceeds from sale of our common stock to collaborators and have the opportunity to earn up to $4.8 billion in potential future milestone payments and additional licensed target fees from our ongoing collaborations and licenses, in addition to potential product royalties.\n\nProduct Pipeline\n\nFigure 1: Our pipeline, subject to adequate additional funding\n\n8\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nCore Neurology Pipeline\n\nChronic Neuropathic Pain – ST-503\n\nWe are developing ST-503, an investigational epigenetic regulator for the treatment of intractable pain due to SFN, a type of chronic neuropathic pain.\n\nNeuropathic pain can be caused by a broad array of pathologies impacting the central or peripheral nervous systems, such as surgical trauma, spinal cord injury, nerve compression, neurological and infectious diseases, or metabolic and hereditary syndromes. ST-503 is not intended for sporadic or acute pain, but for chronic, intractable pain that completely dominates and often destroys the lives of patients over many years.\n\nFollowing FDA clearance of the IND for SFN in November 2024, six clinical sites have been activated for the Phase 1/2 STAND study and patient recruitment and enrollment have commenced. In December 2025, the FDA granted Fast Track Designation to ST-503. 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.\n\nFigure 2: Our approach in SFN using ZFRs\n\nThe Phase 1/2 study is designed to assess the safety and efficacy of ST-503 in addressing SFN, a peripheral neuropathy that results in highly debilitating symptoms of burning, prickling, stabbing or “lightning-like” pain. SFN has an estimated prevalence of at least 180,000 patients in the U.S., and more broadly, peripheral neuropathies are estimated to affect nearly 40 million Americans. Antidepressants, anticonvulsants, opioids and topical therapies are potential treatment options, although no long-lasting or curative therapies are currently available for SFN patients, leading to a high unmet medical need for this patient population.\n\nSubject to our ability to secure adequate additional funding, we intend to conduct a double-blind, randomized, sham-controlled dose escalation study to determine safety and tolerability of a single intrathecal dose of the ST-503 gene therapy for refractory pain due to small fiber neuropathy. The Phase 1/2 STAND study is designed to follow a dose escalation protocol with a 2:1 randomization of investigational product to sham, and consists of three ascending dose cohorts. The primary objectives of the Phase 1/2 study will be to assess the safety and tolerability of ST-503, with secondary objectives to assess\n\n9\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\npreliminary efficacy based on the impact of ST-503 on refractory pain, and assessment of the multidimensional impact of ST-503 on sleep, mental health and quality of life.\n\nA significant body of evidence implicates sodium channels in mediating the pathophysiology of neuropathic pain. ST-503 uses an AAV vector carrying an engineered zinc finger repressor, or ZFR, to specifically target the human gene, SCN9A, that encodes the Nav1.7 sodium channel and is critical for pain signaling. Developing small molecules that specifically target Nav1.7 is challenging due to the high structural similarities between different sodium channels, making it difficult to achieve selectivity and avoid off-target effects. By directly targeting the SCN9A gene, ST-503 was shown to selectively reduce the expression of Nav1.7 sodium channels in sensory neurons in animal models and significantly reduce pain hypersensitivity, following a single intrathecal administration of ST-503. Sangamo’s preclinical research has shown ST-503 to be well tolerated in NHPs, with substantial Nav1.7 reduction observed with no off-target effects, demonstrating the promise of ST-503 as a potential therapy for chronic neuropathic pain, regardless of cause.\n\nPrion Disease\n\nWe are also developing our other lead wholly owned preclinical epigenetic regulation program in prion disease, a fatal and incurable neurodegenerative disease caused by the misfolding of the prion protein encoded by the gene PRNP.\n\nThis misfolding of the prion protein is acutely toxic to neurons, and our aim is to remove a portion of prion protein from neurons to protect them from the toxicity of the misfolded prion protein. We think that this may prevent the spread and propagation of misfolded prion, and may therefore slow or halt neurodegeneration and disease progression.\n\nAt least 1,500 new cases of prion disease are identified each year in the United States, Europe and Japan, with a similar presence globally.\n\nCTA-enabling activities have commenced for ST-506, an investigational epigenetic regulator for the treatment of prion disease, leveraging STAC-BBB, our novel proprietary neurotropic AAV capsid. In 2025, we held productive interactions with the U.K. Medicines and Healthcare products Regulatory Agency, or MHRA, including alignment on nonclinical safety studies, the clinical study design and the Chemistry, Manufacturing and Controls, or CMC, strategy. The Good Laboratory Practice, or GLP, Toxicology study has been completed and analysis is in progress.\n\nFigure 3: Our approach in prion disease using ZFRs\n\nTo address prion disease, we are developing ZFRs that target the PRNP gene, to be delivered by STAC-BBB, our IV-administered neurotropic AAV capsid. We presented updated preclinical data from this program in the prestigious Presidential Symposium at the 28th American Society of Gene & Cell Therapy, or ASGCT, Annual meeting, in May 2025 and at the Prion 2025 Conference in November 2025. The presented data demonstrated the profound survival extension observed in disease mouse models and the sustained widespread brain delivery and prion reduction in NHPs and mice treated with ST-506.\n\n10\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nThe clinical study is expected to be a Bayesian optimal interval design, to assess safety and efficacy, while potentially enabling rapid escalation to the maximum tolerated dose. The clinical study plans to use the Medical Research Council prion disease rating scale to assess the efficacy of the ZFR and compare to matched historic controls. The aim of the planned clinical study is to delay the progression of prion disease, offering potential for a meaningful extension of survival in prion patients.\n\nClinical Programs\n\nIsaralgagene civaparvovec – Fabry Disease\n\nIsaralgagene civaparvovec, or ST-920, is our wholly owned gene therapy product candidate for the treatment of Fabry disease, a rare inherited metabolic disease. Isaralgagene civaparvovec was evaluated in our completed, registrational Phase 1/2 STAAR clinical study, and continues to be evaluated in the subsequent long term follow up study. We believe this product candidate has a clear regulatory pathway to Accelerated Approval from the FDA.\n\nSTAAR was a Phase 1/2 multicenter, open-label, dose-ranging clinical study designed to assess a single infusion of isaralgagene civaparvovec in symptomatic Fabry disease patients ≥ 18 years of age. Patients were infused intravenously with a single dose and followed for 52 weeks. A separate long-term follow-up study is underway to monitor the patients treated in this study for up to five years following treatment to further assess safety, durability and efficacy. Patients who were on stable Enzyme Replacement Therapy, or ERT, could withdraw ERT after treatment in a controlled and monitored fashion at the discretion of the patient and the investigator.\n\nThe dose escalation phase included males with classic Fabry disease. The study was subsequently expanded to enroll both males and females, including patients with Fabry-associated cardiac or renal disease. The study’s primary endpoint was the incidence of treatment-emergent adverse events, or AEs. Secondary endpoints included change from baseline at specific time points over the one-year study period in alpha‑galactosidase A, or α‑Gal A, activity, globotriaosylceramide, or Gb3, and lyso‑Gb3 levels in plasma; frequency of ERT infusion; changes in renal function and cardiac function (left ventricular mass) measured by cardiac magnetic resonance imaging, or MRI, and rAAV2/6 vector clearance. Key exploratory endpoints included change from baseline in disease severity (Fabry Outcome Survey adaptation of the Mainz Severity Score Index, or FOS-MSSI, score), quality of life, or QoL, gastrointestinal, or GI, symptoms and neuropathic pain scores; and immune response to AAV6 capsid and α‑Gal A.\n\n11\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 4: Our approach in Fabry disease\n\nThe goal of the study was to abrogate the need for ERT with a recombinant AAV2/6 vector encoding cDNA for human α‑Gal A, resulting in long-term expression of α‑Gal A. As a liver-directed gene therapy, isaralgagene civaparvovec is designed to be delivered by a one-time IV infusion that does not require any preconditioning regimen for patients.\n\nThe FDA has granted Orphan Drug, Fast Track and regenerative medicine advanced therapy, or RMAT, designations to isaralgagene civaparvovec, which has also received Orphan Medicinal Product designation and PRIME eligibility from the European Medicines Agency, or EMA, and Innovative Licensing and Access Pathway, or ILAP, from the MHRA.\n\nIn October 2024, we announced the outcome of a successful interaction with the FDA that we believe provided a clear regulatory pathway to Accelerated Approval for isaralgagene civaparvovec. The FDA agreed in a Type B interaction that data from the ongoing Phase 1/2 STAAR study can serve as the primary basis for approval under the Accelerated Approval Program, using estimated glomerular filtration rate, or eGFR, slope at 52 weeks across all patients as an intermediate clinical endpoint. The FDA also advised that eGFR slope at 104 weeks may be assessed to verify clinical benefit.\n\nIn October 2025, we held a meeting with the FDA to discuss the proposed efficacy and safety data package for isaralgagene civaparvovec where, in the meeting minutes, among other things, the FDA reiterated its October 2024 agreement to use eGFR slope as an endpoint to support an accelerated approval pathway.\n\nThe dataset to support an Accelerated Approval pathway was completed in the first half of 2025 and in June 2025 we announced positive topline results from the STAAR study, including a positive mean eGFR slope at 52-weeks across all dosed patients in the study, which the FDA has agreed may serve as the primary basis of approval. We believe that the totality of STAAR data demonstrates the potential of isaralgagene civaparvovec as a one-time, well-tolerated and durable gene therapy treatment option for Fabry disease to provide meaningful, multi-organ clinical benefits that could fundamentally shift the Fabry treatment paradigm.\n\n12\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nIn December 2025, we initiated a rolling submission of a BLA to the FDA seeking approval of isaralgagene civaparvovec under an Accelerated Approval pathway and have submitted the preclinical and clinical modules to the FDA for review. Rolling submission allows for completed modules 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. In addition, the antibody assay companion diagnostic, which is designed to screen patients for eligibility with isaralgagene civaparvovec, has been submitted to, and accepted by, the FDA’s Center for Devices and Radiological Health, or CDRH, seeking Premarket Approval, or PMA.\n\nWe continue to develop the Chemistry, Manufacturing and Controls, or CMC, module, ahead of completion of the rolling BLA submission for isaralgagene civaparvovec, currently expected to occur as early as the summer of 2026 subject to our ability to secure adequate additional funding, while we continue early stage business development discussions for a potential Fabry commercialization agreement.\n\nWe continue to engage with the EMA on the proposed pathway to potential approval for isaralgagene civaparvovec in Europe.\n\nWe announced detailed data from the STAAR study via four platform presentations and in poster presentations at the 22nd Annual WORLDSymposiumTM that took place February 2-6, 2026 in San Diego, CA. A summary of the data is below.\n\nSummary of Clinical Data from Registrational Phase 1/2 STAAR Study of Isaralgagene Civaparvovec Announced on February 3, 2026 in Advance of Presentation at 22nd Annual WORLDSymposiumTM, February 2-6, 2026\n\n•As of the April 10, 2025 data cutoff date, 33 patients ranging in age from 18 to 67 years were treated with isaralgagene civaparvovec, nine in the dose escalation phase and 24 in the dose expansion phase of the study. Baseline characteristics of these 33 dosed patients are shown in Table 5 below. In the dose escalation phase, two patients were dosed in Cohort 1 at the dose of 0.26x1013 vg/kg, two patients were dosed in Cohort 2 at the dose of 0.53x1013 vg/kg, three patients were dosed in Cohort 3 at the dose of 1.58x1013 vg/kg, and two patients were dosed in Cohort 4 at the dose of 2.63x1013 vg/kg. In the dose expansion phase, 24 patients were dosed at the dose of 2.63x1013 vg/kg. As of the April 10, 2025 data cutoff date, the median duration of follow-up was 24 months, with the first dosed patient having been followed for at least 54.3 months. 32 dosed patients in the study had achieved at least 52 weeks follow-up as of the April 10, 2025 data cutoff date. Patient 14 withdrew from the study at Week 21 due to personal reasons unrelated to the study.\n\n•As of the April 10, 2025 data cutoff date, isaralgagene civaparvovec continued to be generally well-tolerated across all the dose cohorts, without the need for preconditioning and with the majority of AEs being graded as mild (Grade 1) or moderate (Grade 2) in nature. A summary of the treatment-related AEs reported as of the April 10, 2025 cutoff date is shown in Table 6 below. Treatment-emergent serious AEs, or TESAEs were reported in four patients, all Grade 2 or Grade 3: left arm pain, non-cardiac chest pain, sepsis, stroke and shoulder enthesopathy. The event of shoulder enthesopathy was the only serious adverse event, or SAE, deemed related to treatment. Any liver function test, or LFT, elevation events were Grade 1 and all resolved without clinical sequalae. No Thrombotic Microangiopathy, or TMA, or complement activation events were observed. No AEs led to study discontinuation. No deaths were reported.\n\n•As of the April 10, 2025 data cutoff date, all 15 ERT naïve or pseudo-naïve patients showed normal to supraphysiological levels of α-Gal A activity up to 54 months for the longest treated patient, as shown in Figure 7a. Sustained normal to supraphysiological expression of α-Gal A activity was accompanied by the reduction and/or long-term stabilization of lyso-Gb3 levels, with the largest reductions in plasma lyso-Gb3 seen in patients with the highest levels at baseline, as shown in Figure 7b.\n\n•For patients who began the study on ERT, sustained elevated levels of α-Gal A activity were observed for 17 of the 18 On ERT patients, as shown in Figure 8a. Plasma lyso-Gb3 activity levels remained generally stable following ERT withdrawal, as shown in Figure 8b. Following dosing with isaralgagene civaparvovec, all 18 patients who came into the study on ERT were able to safely withdraw from ERT, with one patient now off ERT for more than four years. Since the data cutoff date, a physician decided to resume ERT for one of their treated patients who had withdrawn from ERT. This patient, who received isaralgagene civaparvovec more than three years ago, maintained supraphysiological levels of α-Gal A activity, and their lyso-Gb3 levels were generally stable as of the April 10, 2025 data cutoff date.\n\n•Two methods were employed to estimate the mean annualized eGFR slope and its 95% confidence interval, or CI. First, individual eGFR slopes at Weeks 52 and 104 were estimated using a linear regression model in a two-step process. Additionally, a mixed model with Random Intercept and Random Slope, or RIRS, was used for estimation. As of the April 10, 2025 data cutoff date, a positive mean annualized eGFR slope of 1.965 mL/min/1.73m2/year (95% CI: -0.153, 4.083) and a positive mean annualized RIRS eGFR slope of 2.020 mL/min/1.73m2/year (95% CI: -0.055, 4.095) at 52-weeks were observed across all 32 dosed patients with 52 week eGFR data. Furthermore, a mean annualized eGFR slope at Week 104 of 1.747 mL/min/1.73m2/year (95% CI: -0.106, 3.601) and a positive mean annualized RIRS eGFR slope of 1.751 mL/min/1.73m2/year (95% CI: -0.053, 3.555) were observed for the 19 patients who have achieved 104-weeks of follow-up, as shown in Figure 9 below. These slopes compare favorably to a meta-analysis of publications of approved Fabry treatments\n\n13\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\n(Fabrazyme, Replagal and Galafold). The mean and 95% CI were calculated with adjustments to age, gender, and baseline eGFR. The upper confidence limit, or UCL, of the 95% CI, -1.055 mL/min/1.73m2/year, was used to rule out variability in data and serves as a conservative historical comparator for Fabry patients treated with approved therapies.\n\n•A subgroup analysis of mean annualized eGFR slopes was performed at Week 52, showing supportive mean annualized eGFR slopes across subgroups such as gender, baseline ERT status, disease type and baseline eGFR compared to the meta-analysis of approved Fabry treatments, and as shown in Figure 10 below, demonstrating consistency in effect across Fabry patients in the study.\n\n•Figure 11 below illustrates the evolution in mean annualized eGFR slopes over time, for 32 patients up to Week 52, 22 patients at 18 months and 19 patients at Week 104. At Week 16, the earliest measurement timepoint, mean eGFR slope across all 32 patients was -3.634 mL/min/1.73m2/year. Improvements in eGFR slope were seen as early as Week 24 following isaralgagene civaparvovec administration, with the mean eGFR slope increasing over time and becoming positive at Week 36. A maximum mean eGFR slope of 3.016 mL/min/1.73m2/year was achieved at 18-months post isaralgagene civaparvovec administration, for 22 patients who had reached this duration of follow-up as of the data cutoff date.\n\n•As of the April 10, 2025 data cutoff date, stable cardiac function was observed. Electrocardiogram, or ECG, and echocardiogram, or ECHO, findings demonstrated stability over 52 weeks, with mean P wave to R wave, or PR, interval, Mean Ventricular Rate, Q wave R wave S wave, or QRS, Interval, Baseline Q wave T wave, or QT, interval, Baseline rate-corrected QT, or QTc, mean interval, Left Ventricular Mass Index, or LVMI, and Ejection Fraction, or EF, indicating clinical stability across the various subgroups, as shown in Table 12 below. QTc interval slightly improved and ventricular wall thickness remained stable. Cardiac structure and function also remained stable over 52 weeks.\n\n•Cardiac MRI also demonstrated preservation of left ventricular structure and systolic function. As of the April 10, 2025 cutoff date, ejection fraction and global longitudinal strain were preserved over 52 weeks, as shown in Table 13 below. Stable Troponin T levels indicated stable myocardial disease and stable N-Terminal ProB-type Natriuretic Peptide levels indicated overall stable cardiorenal function.\n\n•Significant improvements in disease severity, QoL, and GI symptoms were observed. As of the April 10, 2025 data cutoff date, nine patients, including five on ERT, improved their total FOS-MSSI score at 12 months and nine patients improved their FOS-MSSI category compared to baseline at the last assessment. Statistically significant and clinically meaningful improvements in the short form-36, or SF-36, QoL scores were reported for general health, physical component, bodily pain, role-physical, vitality and social functioning scores, as shown in Figure 14 below. The GI symptom rating scale, or GSRS, also demonstrated statistically significant improvements in GSRS and Diarrhea scores at Week 52 compared to baseline.\n\n•Immunogenicity remains an issue with ERT, leading to continued organ impairment. 10 patients had measurable titers of total antibodies, or Tabs, or neutralizing antibodies, or Nabs, against α-Gal A associated with ERT at baseline. As shown in Table 15, following dosing, total TAb or NAb titers decreased markedly in nine patients and became undetectable in eight, or 80% of patients. Treatment did not induce anti-α-Gal A antibodies in baseline seronegative patients.\n\n14\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nTable 5: Baseline characteristics: Dose escalation and dose expansion phases\n\nData cutoff date: April 10, 2025\n\neGFR, estimated glomerular filtration rate (mL/min/1.73m2); ERT, enzyme replacement therapy; n, number, M, male; F, female\n\n15\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nTable 6: Summary of treatment-emergent AEs in >10% of patients\n\nData cutoff date: April 10, 2025\n\nAE, adverse event; G, grade; n, number\n\n16\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 7a: Plasma α-Gal A in ERT naïve/pseudo-naïve patients (n=15)\n\nData cutoff date: April 10, 2025\n\nα-Gal A activity measured using 3-hour reaction time. Normal range determined in healthy males and females. Long Term Follow-up Data: Data points > Study Day 365.\n\nα-Gal A, alpha-galactosidase A; ERT, enzyme replacement therapy; vg/kg, vector genomes per kilogram of total body weight (as assessed by droplet polymerase chain reaction, or ddPCR); n, number\n\n17\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 7b: Lyso-Gb3 in ERT naïve/pseudo-naïve patients (n=15)\n\nData cutoff date: April 10, 2025\n\nLyso-Gb3, globotriaosylceramide; ERT, enzyme replacement therapy; vg/kg, vector genomes per kilogram of total body weight (as assessed by ddPCR); n, number\n\n18\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 8a: Plasma α-Gal A in ERT-treated patients (n=18)\n\nData cutoff date: April 10, 2025\n\nα-Gal A activity measured using 3-hour reaction time. Normal range determined in healthy males and females.\n\nα-Gal A, alpha-galactosidase A; ERT, enzyme replacement therapy; vg/kg, vector genomes per kilogram of total body weight (as assessed by ddPCR); n, number\n\n19\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 8b: Lyso-Gb3 in ERT-treated patients (n=18)\n\nData cutoff date: April 10, 2025\n\nERT, enzyme replacement therapy; lyso-Gb3, globotriaosylsphingosine; vg/kg, vector genomes per kilogram of total body weight (as assessed by ddPCR); n, number\n\n20\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 9: Positive mean eGFR slopes were observed at weeks 52 and 104\n\nData cutoff date: April 10, 2025\n\neGFR, estimated glomerular filtration rate (mL/min/1.73m2); n, number; CI, confidence interval; RIRS, random intercept and random slope; UCL, upper confidence limit\n\nA meta-analysis of publications of approved Fabry treatments (Fabrazyme, Galafold, Replagal) was conducted (Feriozzi 2012, Hughes 2016). The mean and 95% CI were calculated with adjustments to age, gender, and baseline eGFR. The upper confidence limit (UCL) of the 95% CI, -1.055 mL/min/1.73m2/year, was used to rule out variability in data and serves as a conservative historical comparator for Fabry patients treated with approved therapies. One participant discontinued the study with 12 weeks eGFR data, thus not included in the analysis.\n\n21\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 10: Subgroup analysis – mean annualized eGFR slope at week 52\n\nData cutoff date: April 10, 2025\n\neGFR, estimated glomerular filtration rate (mL/min/1.73m2); n, number; UCL, upper confidence limit; CI, confidence interval\n\n22\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 11: Evolution in mean eGFR slope over 24 months\n\nData cutoff date: April 10, 2025\n\neGFR, estimated glomerular filtration rate (mL/min/1.73m2); n, number; m, months\n\nTable 12: ECG and ECHO findings over 52 weeks\n\nData cutoff date: April 10, 2025\n\nEF, ejection fraction; LVMI, left ventricular mass index; QRS, Q wave R wave S wave interval; QT, Q wave T wave interval; QTc, rate-corrected QT interval; PR, P wave to R wave interval; ECG, electrocardiogram; n, number; MM, millimeter; MS, milli second; SD, standard deviation; * p-value > 0.05 for all parameters above\n\n23\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nTable 13: Cardiac MRI results over 52 weeks\n\nData cutoff date: April 10, 2025\n\nLVEF, left ventricular ejection fraction; LVGLMS, left ventricular global longitudinal myocardial strain; n, number; MRI, magnetic resonance imaging; ML, milli liter; NG/L, nanogram per liter; PG/ML, picogram per milliliter; CI, confidence interval\n\n24\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nTable 14: SF-36 scores over 52 weeks\n\nData cutoff date: April 10, 2025\n\nAnalysis of ST-920 treated subjects with ≥12 m follow-up (n=32). “Month 12” is Week 52 study timepoint. All p-values are unadjusted nominal p-values. FOS-MSSI, Fabry outcome survey-mains severity score; SF-36. 36-item short form health survey; GI, gastrointestinal. Best score from up to 4.5 years follow up data.\n\nTable 15: Reduction or elimination of antibodies against α-Gal A\n\nData cutoff date: April 10, 2025\n\nα-Gal A, alpha-galactosidase A; TAb, total antibody; NAb, neutralizing antibody; W, week\n\nGiroctocogene Fitelparvovec – Hemophilia A\n\nAFFINE is a global Phase 3, open-label, multicenter, single arm trial evaluating the efficacy and safety of a single infusion of giroctocogene fitelparvovec, also known as SB-525, an investigational gene therapy that we co-developed with and\n\n25\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nlicensed to Pfizer for the treatment of adults with moderately severe to severe hemophilia A, and to which we regained development and commercialization rights in April 2025. The primary endpoint is impact on annualized bleeding rate, or ABR, through 12 months following treatment with giroctocogene fitelparvovec, compared to ABR on factor VIII, or FVIII, replacement therapy collected in the Phase 3 lead-in study period.\n\nFigure 16: Approach to Hemophilia A\n\nIn July 2024, Pfizer reported that the AFFINE trial achieved its primary objective of non-inferiority, as well as superiority, of total ABR from Week 12 through at least 15 months of follow up post-infusion compared with routine FVIII replacement prophylaxis treatment. Following a single 3e13 vg/kg dose, giroctocogene fitelparvovec demonstrated a statistically significant reduction in mean total ABR compared to the pre-infusion period. Key secondary endpoints as defined by the trial protocol were met and also demonstrated superiority compared to prophylaxis. In the AFFINE trial, giroctocogene fitelparvovec was generally well tolerated.\n\nIn December 2024, Pfizer presented detailed data from the Phase 3 AFFINE trial in an oral presentation at the 66th American Society for Hematology Annual Meeting and Exposition and in a poster presentation. A summary of the data is below.\n\nIn April 2025, we regained development and commercialization rights to giroctocogene fitelparvovec following a decision by Pfizer to terminate the Collaboration and License Agreement dated May 10, 2017, or the Collaboration Agreement.\n\nAs of the Termination Date, the Collaboration Agreement was terminated in its entirety, and we received an exclusive, worldwide, royalty-bearing, sublicensable license from Pfizer to use Pfizer’s relevant intellectual property to continue developing, manufacturing and commercializing giroctocogene fitelparvovec. In return, Pfizer would be eligible to receive low single digit royalties on net sales of giroctocogene fitelparvovec. We have completed the transition of the program back to\n\n26\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nSangamo, and we currently are in business development negotiations with a potential collaboration partner for giroctocogene fitelparvovec.\n\nSummary of Efficacy and Safety of Giroctocogene Fitelparvovec in Adults With Moderately Severe to Severe Hemophilia A: Primary Analysis Results From the Phase 3 AFFINE Gene Therapy Trial\n\n•AFFINE is a global Phase 3, open-label, multicenter, single arm trial evaluating the efficacy and safety of a single infusion of giroctocogene fitelparvovec in 75 adult (ages 18-64 years) male patients with moderately severe to severe hemophilia A.\n\n•The trial enrolled male participants with hemophilia A who had completed a lead-in study while on exogenous FVIII prophylaxis therapy prior to administration of a single infusion of 3e13 vg/kg giroctocogene fitelparvovec. The lead-in trial was initiated to establish prospective bleeding and infusion rates while on FVIII prophylaxis replacement therapy in the usual care setting of participants with hemophilia A. Primary and secondary endpoints were assessed in the efficacy population corresponding to participants with ≥15 months follow-up post-infusion and at least six months follow-up in the lead-in study, as shown in Figure 17 below.\n\n•As of the cutoff date of June 2024, 75 participants (median age, 30 [range 19–59] years) were dosed with giroctocogene fitelparvovec. Of those 75 participants, 50 were included in the efficacy population. See Figure 18 below for baseline patient demographics.\n\n•The primary endpoint was ABR for total (treated and untreated) bleeds from Week 12 (onset of clinically meaningful transgene-derived FVIII levels) through ≥15 months post-infusion compared to the pre-infusion prophylaxis period. Within this efficacy population, the study met its primary endpoint with a statistically significant decrease in total ABR from Week 12 through ≥15 months post-infusion compared to pre-infusion prophylaxis (mean total ABR, 1.24 vs 4.73). 64.0% (32/50) of participants experienced no bleeding events (median duration of follow-up, 33.6 months [range 14.5-44.4]) and 88.0% (44/50) of participants had no treated bleeds (median duration of follow-up, 33.6 months [range 14.5─44.4]). One participant in the efficacy population experienced a high number of bleeds (126, total ABR = 47.4) starting at Month 18 post infusion, while maintaining FVIII activity levels >150% through the data cutoff. Post hoc sensitivity analysis excluding that one participant (n=49) demonstrated superiority vs FVIII prophylaxis (mean total ABR, 0.26 vs 4.65) as shown in Figure 19 below.\n\n•Treated ABR during Week 12 through ≥15 months post-infusion was significantly reduced compared to prophylaxis (mean treated ABR, 0.07 vs 4.08), also demonstrating superiority, as shown in Figure 20 below. AIR post-infusion was reduced by 99.8% compared to the pre-infusion period (mean AIR, 0.21 vs 124.39). As of the June 2024 cutoff date, one (1.3%) dosed participant had resumed prophylaxis (at 16.07 months post-infusion).\n\n•At Month 15, 84% of participants had FVIII activity >5% via chromogenic assay, as shown in Figure 21 below. Participants continued to maintain FVIII activity >5%, with 82.8% of participants [n=29] continuing to maintain FVIII activity >5% at 2-years post-infusion and 63% of participants [n=8] at 3-years post-infusion respectively, as shown in Figure 22 below.\n\n•A total of 624 AEs, mostly mild or moderate, were reported in 74 (98.7%) participants, as shown in Figure 23 below. There were 26 serious AEs, or SAEs, in 15 (20%) participants. The most common treatment-related AEs were pyrexia (54.7% of participants), alanine aminotransferase, or ALT, increased (46.7%), and headache (38.7%). There have been no study discontinuations. As of the data cutoff, there were no reported FVIII inhibitors and no malignancies related to the study drug. One thrombotic event was observed in a participant with a major protocol deviation (prior history of deep vein thrombosis, or DVT, and pulmonary embolism, or PE) and multiple thrombotic risk factors. Post-infusion, 62.7% of participants received at least one dose of corticosteroids due to ALT elevations or decreases in FVIII activity (median time to initiation, 84 [range 7–193] days; mean total time on corticosteroids, 114.6 [11–296] days), as shown in Figure 24 below. Overall corticosteroids were well tolerated with AEs related to corticosteroids reported in 19 (25.3%) participants.\n\n•Transient FVIII activity >150% (defined as ≥1 central chromogenic assay measurement >150%) was reached in 37 (49.3%) participants, with 23 (30.7%) treated with prophylactic direct oral anticoagulants based on protocol and investigator’s recommendation, which was well tolerated, as shown in Figure 25 below.\n\n•In summary, giroctocogene fitelparvovec yielded endogenous FVIII expression in the mild to normal range in most participants, resulting in superior bleed protection versus routine FVIII prophylaxis and significant reductions in bleeding. A single infusion was well tolerated and demonstrated durable efficacy on all primary and key secondary endpoints.\n\n27\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 17: AFFINE study design\n\nAAV-6=adeno-associated virus serotype 6; ABR=annualized bleeding rate; AIR=annualized infusion rate; FVIII=factor VIII; NAb=neutralizing antibody; vg=vector genome\n\nFigure 18: Baseline demographics and characteristics\n\na n (%) unless otherwise noted. BMI=body mass index\n\n28\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 19: Annualized bleeding rate: Total (treated and untreated) bleeds\n\nNumbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participant as a random effect and treatment and duration of follow-up (in years) as fixed effects.\n\nABRtotal=annualized bleeding rate for total (treated and untreated) bleeds; CI=confidence interval; FVIII=factor VIII\n\n29\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 20: Annualized bleeding rate: Treated bleeds\n\nNumbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participant as a random effect and treatment and duration of follow-up (in years) as fixed effects.\n\nABRtreated=annualized bleeding rate for treated bleeds; CI=confidence interval; FVIII=factor VIII\n\n30\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 21: FVIII activity levels post infusion\n\nCA=chromogenic assay; FVIII=factor VIII; LLOQ=lower limit of quantification\n\nFigure 22: FVIII activity levels through Year Three\n\nValues >300% not shown.\n\nCA=chromogenic assay; BLOQ=below lower limit of quantification; FVIII=factor VIII; IQR=interquartile range; max=maximum; min=minimum; Q=quartile\n\n31\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 23: Safety overview\n\nAE=adverse event; AESI=adverse event of special interest; DVT=deep vein thrombosis; FVIII=factor VIII; PE=pulmonary embolism; SAE=serious adverse event\n\n32\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 24: ALT elevations and corticosteroid use\n\na The highest CTCAE grade among all post baseline assessments from each participant are reported.\n\nAE=adverse event; ALT=alanine aminotransferase; CTCAE=common terminology criteria for adverse events; MMF=mycophenolate mofetil; pts=participants; SAE=serious adverse event; ULN=upper limit of normal\n\n33\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nFigure 25: FVIII activity elevations\n\nCA=chromogenic assay; DOAC=direct oral anticoagulant; DVT=deep vein thrombosis; FVIII=factor VIII; OSA=one-stage assay; PD=protocol deviation; PE=pulmonary embolism\n\nOUR TECHNOLOGIES\n\nOur strategy is to translate our differentiated and versatile technology platforms to create product candidates with best- or first-in-class clinical potential. We believe that the versatility and flexibility of our technology platforms enable us to design therapeutic approaches to resolve the underlying genetic or cellular causes of disease, using whichever technology is best suited to deliver that treatment.\n\nZF Platform: Providing Opportunity to Develop a New Class of Human Therapeutics\n\nWe believe that our ZF platform provides a unique and proprietary basis for a potentially broad new class of drugs that have differentiated technical advantages over small-molecule drugs, protein pharmaceuticals, RNA-based therapeutics, conventional gene therapy approaches and other gene and genome editing platforms, potentially enabling us to develop therapies that address a broad range of unmet medical needs. We believe that our ZF genomic medicines have the potential to transform treatment strategies for severe diseases from symptom management to lasting cures.\n\nZFPs: Naturally Occurring Sequence Specific DNA Binding Proteins in Humans\n\nZFPs are naturally-occurring sequence-specific DNA-binding proteins in humans that recognize and bind to a specific DNA sequence within or near a particular gene and causes expression of that gene to be “turned on” (activated) or “turned off” (repressed). ZFPs are the most common class of such naturally occurring proteins in a wide range of organisms from yeast to humans. Functional domains may be added to ZFPs that enable genome editing (with enzymes such as nucleases or integrases) or epigenetic regulation (with activators and repressors) at a specific genomic site determined by the ZFP DNA‑binding domain.\n\nFigure 26: Schematic of the two-domain structure of a zinc finger DNA-binding domain and its functional domain\n\n34\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nConsistent with the structure of natural ZFPs, we take a modular approach to the design of the proteins that we engineer. The DNA-recognition part of our engineered proteins is typically composed of four to six zinc fingers. Each individual finger recognizes and binds to a three or four base-pair sequence of DNA and multiple fingers can be linked together to form a zinc finger array that recognizes longer stretches of DNA, thereby improving specificity. By modifying the amino acid sequence of ZFPs, we can engineer novel zinc finger arrays capable of recognizing the unique DNA sequences of a chosen genomic target.\n\nFigure 27: Schematic of a ZFP and a zinc finger array composed of six ZFPs\n\nThe engineered DNA-binding zinc finger array is then linked to a functional domain. The DNA-binding zinc finger array brings this functional domain to the target of interest. Our ability to use our highly specific ZFPs to precisely target a DNA sequence to a gene of interest provides us with a range of genome editing and epigenetic regulation functionalities that can be applied to multiple cell types.\n\nFigure 28: Examples of genome engineering tools that can be offered by our ZF platform\n\nOur engineered zinc fingers can be attached to a cleavage domain of a restriction endonuclease, an enzyme that cuts DNA, creating a ZFN. When a ZFN binds DNA in the correct orientation and spacing, a cut is introduced into the DNA sequence between the ZF binding sites. This break in the DNA triggers a natural process of DNA repair within the cell, effectively “knocking out” the gene function. ZFN-mediated genome editing can be used to disrupt genes that are involved in disease pathology, such as in sickle cell disease. Our ZF platform can also be used to perform base editing, a novel approach that allows for the conversion of a specific target DNA base into another DNA base without the need for double-stranded breaks. Base editing relies on the use of enzymes that can directly change the DNA sequence, such as a deaminase, which changes a specific base in a single strand of DNA. We have developed a compact base editor architecture that can be targeted with high precision and specificity using ZFs, is small enough for packaging into relevant viral vectors, and achieves high\n\n35\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nlevels of editing that are potentially suitable for therapeutic application. In February 2024, a research paper summarizing the key characteristics of the ZF-base editors was published in Nature Communications.\n\nOur priority focus is to evaluate ZF-transcriptional regulators which have the potential to regulate the expression of a target gene, see Figure 29 below. Zinc finger activators, or ZFAs, are created by attaching a zinc finger array to an activation domain with the aim of increasing the expression of a target gene relative to an untreated cell. Alternatively, ZFRs are created by attaching a zinc finger array to a repression domain in order to down regulate or completely turn off a gene. ZFRs can also be designed to selectively repress expression of a mutant allele while allowing for the expression of the healthy allele. We have several preclinical programs evaluating the potential of ZFRs that have been designed to down-regulate the expression of genes as potential treatments for neurological diseases, including the downregulation of the SCN9A gene that encodes the Nav1.7 sodium channels to treat chronic neuropathic pain, and the repression of prion gene expression to treat prion disease. In addition, we are party to a license agreement with Genentech for tauopathies and one other undisclosed neurologic target.\n\nFigure 29: ZFRs have the potential to regulate the expression of a target gene\n\nDue to their compact size, multiple ZFRs can be combined in a single viral construct to achieve efficient multigene modulation in a single transduction event and without the need for double-strand breaks. As proof of concept for this novel platform, we engineered primary human T cells using multiple ZFRs encoded in a single lentivirus with and without a Chimeric Antigen Receptor, or CAR, to repress expression of several allogeneic engineering targets or checkpoint inhibitors. We demonstrated that ZFRs act with high efficiency and specificity on target genes of choice at both the RNA and the protein level.\n\n36\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nNovel AAV Capsid Delivery Platform: Engineering AAVs to target the CNS\n\nWe are evaluating several potential routes of administration for our CNS-targeted investigational therapies, as delivery of genomic medicines to the CNS is a significant obstacle to developing potential therapies treating neurological disorders.\n\nFigure 30: Potential routes of administration to target the central nervous system\n\nSeveral AAV serotypes, most notably benchmark capsid AAV9, distribute to the brain but require high doses to achieve limited expression. We have developed a proprietary AAV capsid engineering platform, SIFTER, with the aim of engineering capsids with improved CNS transduction. We are applying SIFTER to screen tens of millions of unique capsids in order to identify certain capsids that mediate superior delivery to the CNS. Successive rounds of screening are conducted to find capsids that reproducibly demonstrate a desired therapeutic profile.\n\nFigure 31: Sangamo’s proprietary SIFTER platform to develop novel AAV capsids targeting the CNS\n\nIn May 2022, we presented results obtained with the SIFTER platform for CSF administration. This platform notably allowed us to identify new capsids exhibiting improved delivery relative to benchmark capsid AAV9 when delivered intrathecally: STAC-102 and STAC-103 (STAC = Sangamo Therapeutics AAV Capsid).\n\n37\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nIn March 2024, we announced data for our proprietary AAV capsid variant, STAC-BBB, which demonstrated an ability to cross the BBB in NHPs and mediated robust transduction, transgene expression, and targeted, potent epigenetic repression throughout the brain and spinal cord of NHPs after IV administration. STAC-BBB also demonstrated industry-leading brain tropism and enrichment in NHPs, resulting in 700-fold higher transgene expression than the benchmark capsid AAV9 and outperformed all other known published neurotropic capsid variants evaluated in the preclinical study.\n\nFigure 32: In vivo library evaluation in cynomolgus macaques identifies STAC-BBB as the top performing BBB-penetrant capsid for delivery to the brain\n\nSTAC-BBB demonstrated robust penetration of the BBB and widespread transgene expression throughout the brain of NHPs, including in key regions integral to neurological disease pathology such as Alzheimer’s disease, Parkinson’s disease, ALS, Huntington’s disease and other neurodegenerative, neurodevelopmental, neuromuscular, and neuropsychiatric diseases with a defined neurogenetic etiology.\n\nFigure 33: STAC-BBB shows widespread neuronal transduction across all cortical regions\n\nSTAC-BBB mediated robust expression of zinc finger cargo in neurons, the key cell type to target for treatment of neurological diseases. Moreover, results were highly consistent across all animal subjects. The capsid-enabled delivery of zinc finger payloads resulted in the repression of prion and tau genes across key brain regions, offering potential for modification of disease progression in prion disease and various tauopathies. STAC-BBB biodistribution was enriched in the CNS and\n\n38\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nde‑targeted from the liver, dorsal root ganglia, or DRG, and other peripheral organs. We believe this biodistribution profile is optimal for treatment of neurological diseases with AAV-based treatments.\n\nSTAC-BBB was generally well tolerated in NHPs, with no notable treatment related pathological findings in brain, spinal cord and peripheral tissues. We believe STAC-BBB is manufacturable at commercial scale using standard cell culture and purification processes, is soluble using known excipients, and can be characterized using available analytics.\n\nIn May 2025, we presented updated data at ASGCT demonstrating sustained, widespread brain delivery and prion reduction in NHPs treated with ST-506 delivered via STAC-BBB. For the first time we also presented data showing brain-wide delivery in mice following STAC-BBB administration. The latest data further suggests a high potential for human translation with STAC-BBB.\n\nWe believe that improved AAV capsids with higher delivery efficiency and specificity for target tissues have the potential to facilitate development of safe and effective genomic medicines to treat CNS disorders.\n\nSTAC-BBB is the subject of current license agreements with each of Genentech, Astellas and Lilly.\n\nModular Integrase Platform\n\nBuilding on Sangamo’s deep expertise in protein-DNA interactions derived from its zinc finger platform, the MINT platform is a versatile, protein-guided genome editing method designed to integrate large sequences of DNA into the genome to potentially treat – with a single medicine – many different patients who have unique mutations in the same gene.\n\nThe MINT platform utilizes Bxb1, a serine integrase, to integrate large sequences of DNA into the genome and is intended to avoid double stranded DNA breaks as well as the need for assistance from ancillary genome editing or DNA-repair modulating cargo. This flexible approach is cell-type agnostic, has been engineered to be simpler to manufacture than most other targeted integration technologies and is compatible with several delivery modalities including viral, lipid nanoparticle, or LNP delivery and ex vivo electroporation. With minimal dependence on cell DNA repair machinery, we believe the MINT platform carries a reduced translocation risk and our preclinical data have demonstrated high levels of on-target integration in certain locations.\n\nIn May 2025, at ASGCT we presented updated MINT data and in September 2025 we published an updated manuscript describing advances in MINT functionality in bioRxiv. These results demonstrated high-efficiency transgene integration in T cells, along with substantial improvements in activity and specificity achieved through zinc finger fusions to the Bxb1 integrase. To date, by combining zinc finger targeting with activity-enhancing amino acid substitutions in Bxb1, we have achieved transgene integration and expression in up to 45% of T cells.\n\nBased on these initial findings, we believe the MINT platform could be deployed internally for neurology-focused indications, and could provide potential new collaboration opportunities, both for human disease and in agricultural biotech settings.\n\nCurrent Licenses, Partnerships and Collaborations\n\nWe have entered into strategic collaborations with larger biopharmaceutical companies for certain of our therapeutic programs, licenses to our novel AAV capsid, STAC-BBB, and other partnerships for several non-therapeutic applications of our technology. We will continue to pursue further collaborations when appropriate to fund internal research and development activities and to assist in product development, manufacturing, regulatory approval and commercialization. Decisions to collaborate or not will be based on review of our internal resources, institutional knowledge and commercial considerations.\n\nGenentech, Inc.\n\nOn August 2, 2024, we entered into a global epigenetic regulation and capsid delivery license agreement, or the Genentech Agreement, with Genentech to develop intravenously administered genomic medicines to treat certain neurodegenerative diseases. Under the Genentech Agreement, we granted an exclusive license to Genentech for our ZFRs that are directed to tau and a second undisclosed neurology target. We also granted an exclusive license to Genentech to STAC-BBB for use with therapies directed to tau or to the second neurology target.\n\nUnder the Genentech Agreement, we have received from Genentech $50.0 million in an upfront license fee and a milestone payment. In addition, we are eligible to earn up to $1.9 billion in development and commercial milestones spread across multiple potential products under the Genentech Agreement and tiered mid-single digit to sub-teen double digit royalties on the net sales of such products, subject to certain specified reductions.\n\n39\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nAstellas Gene Therapies, Inc.\n\nOn December 18, 2024, we entered into a global epigenetic regulation and capsid delivery license agreement, or the Astellas Agreement, with Astellas to develop intravenously administered genomic medicines to treat certain neurodegenerative diseases. Under the Astellas Agreement, we granted a worldwide exclusive license to Astellas to utilize our STAC-BBB capsid for one target, with the right for Astellas to add up to four additional targets after paying us additional licensed target fees.\n\nUnder the Astellas Agreement, we received from Astellas a $20.0 million upfront license payment. In addition, we are eligible to earn up to $1.3 billion in additional licensed target fees and milestone payments across the five potential neurology disease targets under the Astellas Agreement, as well as tiered mid-to-high single digit royalties on the net sales of any resulting products, subject to certain specified reductions and other conditions.\n\nCapsid Delivery License Agreement with Eli Lilly and Company\n\nOn April 3, 2025, we entered into a global capsid delivery license agreement with Lilly, or the Lilly Agreement, to develop intravenously administered genomic medicines to treat certain diseases of the CNS. Under the Lilly Agreement, we granted a worldwide exclusive license to Lilly to utilize our STAC-BBB capsid for one target, with the rights for Lilly to add up to four additional targets after paying us additional licensed target fees.\n\nUnder the Lilly Agreement, we received from Lilly an $18.0 million upfront license payment. In addition, we are eligible to earn up to $1.4 billion in additional licensed target fees and milestone payments across the five potential targets, as well as tiered royalties on the potential net sales of any resulting products, subject to certain specified reductions and other conditions.\n\nAlexion Pharmaceuticals, Inc. – ALS and Frontotemporal Lobar Degeneration\n\nWe and Pfizer entered into an exclusive, global collaboration and license agreement in December 2017 to develop preclinical genome engineering product candidates that use allele-specific ZF-transcriptional repressors to treat ALS and frontotemporal lobar degeneration, or FTLD, linked to mutations in the C9ORF72 gene. The most frequent genetic cause of ALS is the expansion of hexanucleotide repeats, or G4C2 repeats, in the first intron of the C9ORF72 gene.\n\nIn October 2023, Pfizer notified us that it had assigned to Alexion the collaboration and license agreement between Sangamo and Pfizer for the development and commercialization of potential gene therapy products that use ZF-transcriptional regulators, to treat ALS and FTLD linked to mutations of the C9ORF72 gene.\n\nTakeda – Huntington’s Disease\n\nIn January 2012, we entered into a collaboration and license agreement with Shire International GmbH, a wholly owned subsidiary of Takeda, which we amended and restated in September 2015, to research, develop and commercialize human therapeutics and diagnostics for monogenic diseases based on our ZF technology. We and Takeda developed genome engineering product candidates to treat Huntington’s Disease that use a ZFR designed to differentially down regulate the mutated disease-causing huntingtin gene, or HTT gene, while preserving the expression of the normal version of the gene. Pursuant to the amended and restated agreement, Takeda has an exclusive, worldwide license to ZF therapeutics for treating Huntington’s disease.\n\nOther Partnerships\n\nIn addition to our partnerships for the development of human therapeutic applications, we have also licensed our technology in several other areas, such as plant agriculture and research reagents, including the production of transgenic animals and cell-line engineering. These license partners include Corteva AgriScience, formerly known as Dow AgroSciences LLC, or DAS, Sigma-Aldrich Corporation (now MilliporeSigma in the United States and Merck KGaA outside the United States), and Open Monoclonal Technology, Inc. (now Ligand Pharmaceuticals Incorporated).\n\nINTELLECTUAL PROPERTY\n\nPatents, trade secrets, know-how and licensed technologies are important to our business. Our strategy includes filing, obtaining, maintaining, licensing, and when necessary, defending our patents and patent applications to protect technologies, inventions, and improvements to inventions that we consider important for the research, development, and commercialization of our technologies and our product candidates. We have filed numerous patent applications with the U.S. Patent and Trademark Office, or USPTO, and with patent offices in multiple foreign jurisdictions. Our proprietary intellectual property includes methods relating to the design of ZFPs, Transcription Activator-Like Effector, or TALE, proteins and CRISPR/Cas editing systems, therapeutic applications of genome editing technology, viral vector delivery platforms, enabling technologies related to our platform and the use of genome editing across a variety of applications. We rely on a combination of patents, copyrights, trademarks, proprietary know-how, continuing technological innovations and trade secret protections, as well as confidentiality\n\n40\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nagreements, materials transfer agreements, research agreements and licensing agreements, to establish and protect our proprietary rights.\n\nIn-licensed Technology\n\nWe have exclusively licensed in relevant fields certain intellectual property directed to the design, selection, and use of ZFPs and ZFNs for genome editing from academic institutions. Although no individual in-license is material to our overall protection of our ZFP and ZFN platforms, we believe that these in-licenses, in combination with our own know-how, patent applications and patents, may help protect us from unauthorized third parties who might try to copy or use our products or technologies.\n\nOur Intellectual Property\n\nIn addition to our in-licensed patent portfolio, we have numerous issued patents and pending patent applications comprising approximately 110 patent families that are directed to the design, compositions and uses of ZFPs, ZFNs, ZF-transcriptional factors, TALE proteins and CRISPR/Cas editing systems, viral vector delivery platforms, targeted gene therapies for genetic, metabolic and neurology diseases and disorders, cell therapies for autoimmune disorders, recombinases, integrases, base editors and other technologies related to our programs.\n\nGiven our over two-decade history with zinc finger technology, some of the earliest zinc finger patents in our portfolio began expiring in 2015. However, we have continued to build on this patent portfolio and have been issued additional patents and have applications pending that provide protection for our ZF technology, therapeutic programs, modular integrase and capsid delivery technologies. Additionally, patents that may be issued from our pending applications will extend the patent exclusivity of our patent estate.\n\nWe believe that our in-licensed and our owned patents and patent applications, in combination with our know-how and trade secrets, in the aggregate, will provide us with substantial protection of and exclusivity around the commercial development of our gene therapy and genome engineering programs. In this regard, patents issued to us, applied for by us, or exclusively and non-exclusively licensed to us, cover our commercially relevant technologies, including the following types of inventions, processes and products:\n\n•ZFP and ZFN design, engineered nucleases, and compositions (multiple patents issued with expected expiration dates ranging from 2029 to 2036), absent any PTA, PTE or disclaimers): These patents cover inventions including DNA target site selection, zinc finger binding domain design, nuclease domain design, linker design, DNA nickases, ZFP libraries databases and methods of construction, as well as methods to increase zinc finger binding specificity (see, e.g., US9982245, US10066242, US10113207);\n\n•Nuclease Therapeutics (multiple patents issued with expected expiration dates ranging from 2031 to 2036, absent any PTA, PTE or disclaimers): These patents cover inventions including treatments for hemophilia inherited metabolic diseases, genome editing, regulation of the expression of PD1; Immunomodulatory therapeutics; CNS disease; Modified T cells, including HLA knock out and methods of editing stem cells (see, e.g., US10081661, US10143760); and\n\n•Capsid Delivery Technologies (multiple patent families covering proprietary capsid technologies, having expected expiration dates ranging from 2040 to 2045, absent any PTA, PTE or disclaimers): We have multiple patent families directed to novel AAV capsid sequences, including our proprietary STAC-BBB, STAC-102, and STAC-103, and variants thereof, for the delivery of genome engineering molecules and gene therapy molecules. We also have a patent family (having an expected expiration date of 2045, absent any PTA, PTE, or disclaimers) directed to an identified potential cellular receptor for our proprietary STAC-BBB.\n\nThe patent positions of biopharmaceutical companies, including our patent position, are uncertain and involve complex legal and factual questions for which important legal tenets are largely unresolved and are subject to administrative, judicial, and regulatory interpretation and refinement. Obtaining, maintaining, and enforcing patent protection in the United States and other countries remains uncertain and depends, in part, upon decisions of the patent offices, courts, administrative bodies and lawmakers in these countries. It is also possible that we may develop proprietary products or technologies in the future that are not patentable. Patent applications may not result in the issuance of patents and the coverage claimed in a patent application may be significantly reduced before a patent is issued. It is possible that, under certain circumstances, patent applications will be rejected and we subsequently abandon them. It is possible that we may decide that an issued patent or pending patent application may provide us with little or no competitive advantage in view of its associated costs, in which case we may abandon or allow to lapse such patent or patent applications. Although we have filed for patents on some aspects of our technology, we cannot provide assurances that patents will be issued as a result of these pending applications or that any patent that has been or may be issued will be upheld. It is possible that our current patents, or patents which we may later acquire, may\n\n41\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nbe successfully challenged, invalidated in whole or in part, or deemed unenforceable. The laws of some foreign countries may not protect our proprietary rights to the same extent as do the laws of the United States.\n\nObtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements. Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and/or applications will be due to be paid to the USPTO and various governmental patent agencies outside of the United States in several stages over the lifetime of the patents and/or applications. We have systems in place to remind us to pay these fees, and we employ an outside firm and rely on our outside counsel to pay these fees due to non-U.S. patent agencies. The USPTO and various non-U.S. governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. We employ professionals to help us comply, and in many cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules. However, there are situations in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, our competitors might be able to enter the market and this circumstance would have a material adverse effect on our business.\n\nWe may not be able to protect our intellectual property rights throughout the world. Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States. Ultimately, patent protection must be sought on a country-by-country basis, which is an expensive and time-consuming process with uncertain outcomes. Accordingly, we may choose not to seek or maintain patent protection in certain countries, and we will not have the benefit of patent protection in such countries.\n\nMany companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets and other intellectual property protection, particularly those relating to biotechnology products, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not be able to prevent, alone or with our licensors, misappropriation of our intellectual property rights, particularly in countries where the laws may not protect those rights as fully as in the United States. Many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In addition, many countries limit the enforceability of patents against third parties, including government agencies or government contractors. In some countries, the patent owner may have limited remedies, which could materially diminish the value of such patent. If we or any of our licensors is forced to grant a license to third parties with respect to any patents relevant to our business, our competitive position may be impaired, and our business, financial condition, results of operations, and prospects may be adversely affected.\n\nIn the future, third parties may assert patent, copyright, trademark, and other intellectual property rights to technologies that are important to our business. The outcome following any potential legal assertions of infringement, invalidity and unenforceability is unpredictable. Any claims asserting that our products infringe or may infringe proprietary rights of third parties, if determined adversely to us, could significantly harm our business. See “Risk Factors—Risks Relating to Our Intellectual Property.”\n\nCOMPETITION\n\nWe and our biopharmaceutical collaborators are leaders in the research and development of gene therapies, cell therapies and genome engineering therapies using ZF DNA-binding proteins.\n\nWe are aware of several other companies focused on other methods for editing genes and regulating gene expression and a limited number of commercial and academic groups pursuing the development of ZF genome engineering technologies. The fields of gene therapy and genome engineering are highly competitive, and we expect competition to persist and intensify in the future from a number of different sources, including other biopharmaceutical companies; academic and research institutions; and government agencies that will seek to develop ZFs as well as technologies that will compete with our ZF technology platform, such as TALE proteins and the CRISPR-Cas editing system.\n\n42\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nAccordingly, our competitors may succeed in obtaining patent protection, receiving FDA approval or commercializing competitive products before we do. If we commence commercial product sales, we may be competing against companies with greater marketing, sales, distribution and manufacturing capabilities, areas in which we have limited or no experience. In addition, any product candidate that we successfully develop may compete with existing products that have long histories of safe and effective use.\n\nAlthough we are in the clinical development phase of operations and have no current therapeutic product sales, we believe the following companies, products and/or technologies may potentially be competitive with our technology or our product candidates under development:\n\n•Protein pharmaceuticals under development at pharmaceutical and biotechnology companies such as F. Hoffman-LaRoche Ltd., Protalix Biotherapeutics, Inc., Sanofi S.A. and numerous other biopharmaceutical firms.\n\n•Gene therapy companies developing gene-based products in clinical trials such as BioMarin Pharmaceutical, Inc., F. Hoffman-LaRoche Ltd. through their wholly owned subsidiary Spark Therapeutics, Spur Therapeutics Limited, Exegenesis Bio Co. and 4D Molecular Therapeutics, Inc. and numerous other gene therapy companies.\n\n•Nuclease and base editing technologies under development for therapeutic applications of genome modification including companies such as Caribou Biosciences, Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., Intellia Therapeutics, Inc. and Beam Therapeutics developing the CRISPR/Cas editing system, Cellectis S.A. developing TALE nucleases and meganucleases, and Precision BioSciences, Inc. developing meganucleases and numerous other gene editing companies.\n\n•Antisense therapeutics and RNA interference technology, including RNAi and microRNA, which are technologies that may compete with ours in the development of novel therapeutic products acting through the regulation of gene expression. These technologies are being developed by several companies including Alnylam Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Moderna, Inc., Regulus Therapeutics Inc., Voyager Therapeutics, Inc., Wave Life Sciences, Inc. and numerous other companies.\n\n•Small molecules in development by pharmaceutical companies such as Biogen, Inc., Pfizer, Inc., Vertex Pharmaceuticals, Inc. and numerous other companies.\n\n•AAV capsid technologies developed by companies such as 4D Molecular Therapeutics, Affinia Therapeutics Inc., Capsida Biotherapeutics, Dyno Therapeutics, Inc., StrideBio, Inc., Voyager Therapeutics, Inc. and numerous other companies.\n\nWe expect to face intense competition from other companies for collaborative arrangements with biopharmaceutical companies, for establishing relationships with academic and research institutions, for licenses to proprietary technology and for subjects in our clinical trials of treatments for rare diseases. These competitors, either alone or with their collaborative partners, may succeed in developing technologies or products that are more effective or less costly than ours.\n\nOur ability to compete successfully will depend, in part, on our ability to:\n\n•develop safe, efficacious and commercially attractive proprietary products;\n\n•obtain access to gene transfer technology on commercially reasonable terms;\n\n•obtain required regulatory approvals;\n\n•obtain reimbursement for our products in approved indications;\n\n•attract and retain qualified scientific and product development personnel;\n\n•enter into collaborative and strategic partnerships with others, including our competitors, to develop our technology and product candidates;\n\n•obtain and enforce patents, licenses or other proprietary protection for our products and technologies;\n\n•formulate, manufacture, market and sell any product that we develop;\n\n•develop and maintain products that reach the market first and are technologically superior to or are of lower cost than other products in the market; and\n\n•recruit patients into our clinical trials in a timely fashion.\n\nMANUFACTURING\n\nWe are substantially reliant on external partners to manufacture preclinical and clinical supply for our neurology portfolio. We operate in-house analytical and process development capabilities.\n\n43\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nWe rely on contract manufacturing organizations, or CMOs, to produce our preclinical and clinical AAV product candidates in accordance with FDA and EMA regulations, leveraging current Good Manufacturing Practices, or cGMPs. We employ a technical operations staff in the areas of process development, analytical development, quality control, quality assurance, supply chain, project management, and external manufacturing to facilitate appropriate transfer to and oversight of our CMOs, support our regulatory filings, and supply our clinical trials.\n\nWe currently leverage a distinct manufacturing platform for AAV vector production for our genome engineering and gene therapy product candidates. We use both a commercial scale insect-based baculovirus manufacturing platform and a clinical scale HEK293 mammalian platform to manufacture our various AAV vectors for genome editing and gene therapy, with each AAV vector packaging a different transgene specific to the target indication or ZFN.\n\nGOVERNMENT REGULATION\n\nWe operate within the heavily regulated biopharmaceutical industry and much of our operations, including nonclinical and clinical trials, development, manufacturing, commercialization, marketing and reimbursement are subject to regulatory approvals. Relevant regulatory authorities include, but are not limited to, the FDA, the EMA, the European Commission, national competent authorities of the European Union, or EU, Member States and the MHRA.\n\nProduct Regulation\n\nIn the United States, the FDA regulates biologic products including gene therapy and human cellular therapy products under the Federal Food, Drug, and Cosmetic Act, or the FDCA, the Public Health Service Act, or the PHSA, and regulations and guidance implementing these laws. The FDCA, PHSA and their corresponding regulations govern, among other things, the testing, manufacturing, safety, efficacy, labeling, packaging, storage, record keeping, distribution, reporting, advertising and other promotional practices involving biologic products. Applications to the FDA are required before conducting human clinical testing of biologic products. FDA approval also must be obtained before marketing of biologic products. In the EU, approval from the competent authorities of EU Member States must be obtained before commencing clinical trials. In addition, medicinal products can only be marketed if a marketing authorization, or MA, from the competent regulatory agencies has been obtained.\n\nThe process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes, regulations and applicable guidance require the expenditure of substantial time and financial resources and we may not be able to obtain the required regulatory approvals.\n\nU.S. Biologic Products Development Process\n\nOur product candidates must be approved by the FDA before they may be legally marketed in the United States. The process required by the FDA before a biologic product candidate may be marketed in the United States generally involves the following:\n\n•completion of preclinical laboratory tests and in vivo studies in accordance with the FDA’s current Good Laboratory Practice, or GLP, regulations and applicable requirements for the humane use of laboratory animals or other applicable regulations;\n\n•submission to the FDA of an IND application, which allows human clinical trials to begin unless the FDA objects within 30 days;\n\n•approval by an independent institutional review board, or IRB, reviewing each clinical site before each clinical trial may be initiated;\n\n•performance of adequate and well-controlled human clinical trials according to the FDA’s Good Clinical Practice, or GCP, regulations, and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed biologic product candidate for its intended use;\n\n•preparation and submission to the FDA of a BLA for marketing approval that includes substantial evidence of safety and efficacy from results of nonclinical testing and clinical trials and payment of user fees, if applicable;\n\n•review of the product by an FDA advisory committee, if applicable;\n\n•satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the biologic product candidate is produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the biologic product candidate’s identity, safety, strength, quality, potency and purity;\n\n44\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\n•potential FDA inspection of the nonclinical and clinical trial sites that generated the data in support of the BLA; and\n\n•FDA review and approval, or licensure, of the BLA.\n\nBefore testing any biologic product candidate in humans, including a gene therapy product candidate, the product candidate must undergo preclinical testing. Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of product chemistry, toxicity and formulation, as well as in vivo studies to assess the potential safety and activity of the product candidate and to establish a rationale for therapeutic use. The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs.\n\nConcurrent with clinical trials, companies usually must complete additional preclinical testing, that may include animal tests of reproductive adverse events and carcinogenicity, and must also develop additional information about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the drug in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the drug candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug product. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the drug candidate does not undergo unacceptable deterioration over its shelf life.\n\nHuman gene transfer protocols are subject to the FDA’s oversight and other clinical trial regulations, and oversight at the local level as set forth in National Institutes of Health, or NIH, Guidelines. Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes evaluation and assessment by an institutional biosafety committee, or IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution. The IBC assesses the safety of the research and identifies any potential risk to public health or the environment, and such review may result in some delay before initiation of a clinical trial. Compliance with the NIH Guidelines is mandatory for investigators at institutions receiving NIH funds for research involving recombinant DNA. However, many companies and other institutions, not otherwise subject to the NIH Guidelines, voluntarily follow them.\n\nThe clinical trial sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. Some preclinical testing may continue even after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. The FDA also may impose clinical holds on a biologic product candidate at any time before or during clinical trials due to safety concerns or non-compliance. If the FDA imposes a clinical hold, trials may not recommence without FDA authorization and then only under terms authorized by the FDA. Accordingly, we cannot be sure that submission of an IND will result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise that suspend or terminate such studies.\n\nEU Drug Development Process\n\nSimilar to the United States, the various phases of preclinical and clinical research in the EU are subject to significant regulatory controls. Certain preclinical (also termed “non-clinical”) data is required in order to enable clinical trials and later be used in dossier for a marketing authorization application, or MAA. All studies should be conducted in accordance with GLP and all applicable EMA, European Commission and European Pharmacopoeia guidelines related to preclinical studies, including guidance on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells.\n\nThe requisite amount of preclinical data enables the design of a clinical trial, from Phase 1 (first-in-human clinical trials) through to Phases 2 and 3, which are quality, safety and efficacy studies. Similar restrictions and requirements apply as in the United States regarding preclinical data to support trials using viral vectors. The preclinical tests should establish parameters such as toxicity, pharmacodynamics and pharmacokinetic properties, as well as the quality of the gene therapy medicinal products. Due to the particular nature of gene therapy medicinal products, it is recognized that it may not always be possible for the non-clinical safety studies to be in conformity with the principles of GLP and a proper justification should be submitted where a pivotal non-clinical safety study has not been conducted under GLP rules.\n\nClinical studies are crucial to obtaining the required data and the requirements governing the conduct of clinical trials are further analyzed below.\n\nAll medicinal products and advanced therapy medicinal products, or ATMPs, must be manufactured in accordance with the guidelines on GMP and in a GMP licensed facility, which can be subject to GMP inspections.\n\nHuman Clinical Trials\n\nClinical trials involve the administration of the biologic product candidate to patients under the supervision of qualified investigators which generally are physicians not employed by, or under, the control of the trial sponsor. Clinical trials\n\n45\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nare conducted under written study protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur. Each protocol and any amendments to the protocol must be submitted to the FDA as part of the IND. Clinical trials must be conducted and monitored in accordance with the FDA’s regulations comprising the GCP requirements, including the requirement that all research subjects provide informed consent.\n\nFurther, each clinical trial must be reviewed and approved by an IRB at or servicing each institution at which the clinical trial will be conducted. An IRB is charged with protecting the welfare and rights of trial participants and considers items such as whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the form and content of the informed consent that must be signed by each clinical trial subject, or their legal representative, reviews and approves the study protocol, and must monitor the clinical trial until completed.\n\nHuman clinical trials typically are conducted in three sequential phases that may overlap or be combined:\n\n•Phase 1. The biologic product candidate initially is introduced into a small number of human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early understanding of its effectiveness. Phase 1 clinical trials of gene and cell therapies are typically conducted in patients rather than healthy volunteers.\n\n•Phase 2. The biologic product candidate is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product candidate for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule.\n\n•Phase 3. Phase 3 clinical trials are commonly referred to as “pivotal” studies, which typically denotes a study which presents the data that the FDA or other relevant regulatory agency will use to determine whether or not to approve a biologic product. In Phase 3 studies, the biologic product candidate is administered to an expanded patient population, generally at multiple geographically dispersed clinical trial sites in adequate and well-controlled clinical trials to generate sufficient data to statistically confirm the efficacy and safety of the product for approval. These clinical trials are intended to establish the overall risk/benefit ratio of the product candidate and provide an adequate basis for product labeling.\n\nPost-approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial approval. These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. Sometimes approval for a product is conditional upon the completion of post-marketing clinical studies.\n\nDuring all phases of clinical development, regulatory agencies (such as the FDA, the EMA, national competent authorities of EU Member States and other comparable regulatory agencies) require extensive monitoring and auditing of all clinical activities, clinical data and clinical trial investigators. Annual progress reports detailing the results of the clinical trials must be submitted to the FDA.\n\nWritten IND safety reports must be promptly submitted to the FDA and the investigators for: serious and unexpected adverse events; any findings from other trials, in vivo laboratory tests or in vitro testing that suggest a significant risk for human subjects; or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life‑threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.\n\nThe FDA and comparable foreign regulatory authorities or the sponsor or its data safety monitoring board may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable safety risk. Similarly, an IRB and comparable foreign regulatory authorities can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s or comparable foreign regulatory authority’s requirements or if the biologic product candidate has been associated with unexpected serious harm to patients.\n\nThe FDA and comparable regulatory authorities in the EU usually recommend that sponsors observe subjects for potential gene therapy-related delayed adverse events for up to a 15-year period.\n\nIn the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014, or the CTR, which entered into application on January 31, 2022. The CTR is intended to harmonize and streamline CTAs, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase clinical trial transparency. Specifically, the CTR, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the\n\n46\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nClinical Trials Information System, or CTIS, a single set of documents to be prepared and submitted for the application, as well as simplified reporting procedures for clinical trial sponsors. A harmonized procedure for the assessment of applications for clinical trials has been introduced and is divided into two parts. Part I assessment is led by the competent authorities of a reference Member State selected by the trial sponsor and relates to clinical trial aspects that are considered to be scientifically harmonized across EU Member States. This assessment is then submitted to the competent authorities of all the concerned Member States in which the trial is to be conducted for their review. Part II is assessed separately by the competent authorities and ethics committees in each concerned EU Member State. Individual EU Member States retain the power to authorize the conduct of clinical trials in their territory. All ongoing trials are now subject to the provisions of the CTR.\n\nIf the medicinal product is considered to be a genetically modified organism, or GMO, then GMO approval may also be required from the national GMO competent authorities of EU Member States. There is no harmonization between EU Member States regarding the approach to and timelines of GMO approval, which may result in diverging requirements between EU Member States. In addition, the submission of applications for approval of GMOs to national competent authorities of EU Member States is not made in tandem with applications for the approval of clinical trials that must be submitted via CTIS. As a result, sponsors of clinical trials that include GMOs requiring separate approval cannot benefit from submission of a single application dossier for the approval of a clinical trial and the subsequent synchronized response from EU Member States. This may impact study initiation in a given country.\n\nThe conduct of clinical trials should follow the approved clinical trial protocol, informed consents requirements, including patient informed consents, procedures and controls designed and approved for such studies, accepted standard medical and scientific research procedures and be conducted in accordance with the relevant principles of GCP and all applicable laws and regulations. Gene therapy medicinal products are in addition subject to the rules of GCP for ATMPs, which outline specific additional safeguards and requirements. Record retention requirements are increased for ATMPs as there are relevant long term follow-up and human safety and traceability requirements.\n\nCompliance with cGMP Requirements\n\nManufacturers of biologics must comply with applicable current cGMP regulations, including quality control and quality assurance and maintenance of records and documentation. Manufacturers and others involved in the manufacture and distribution of such products also must register their establishments with the FDA and certain state agencies, as well as foreign authorities including the competent authorities of the EU Member States. Both domestic and foreign manufacturing establishments must register and provide additional information to the FDA, as well as foreign authorities including the competent authorities of the EU Member States, upon their initial participation in the manufacturing process. Any material changes to the manufacturing equipment, process or location of the approved manufacturing site must be reported to the relevant agency/authority. Establishments may be subject to periodic, unannounced inspections by government authorities (including regulatory agencies) to ensure compliance with cGMP requirements and other laws. Discovery of problems may result in a government entity placing restrictions on a product, manufacturer or holder of an approved BLA or authorization for clinical trial, and may extend to requiring withdrawal of the product from the market, issue warning or similar letters or seeking civil, criminal or administrative sanctions against the company. The FDA and foreign authorities including the competent authorities of the EU Member States will not approve a BLA unless they determine that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specification.\n\nConcurrent with clinical trials, companies develop additional information about the physical and biological characteristics of the product candidate as well as finalize a process for manufacturing the product candidate in commercial quantities in accordance with cGMP requirements. To help reduce the risk of the introduction of adventitious agents or of causing other adverse events with the use of biologic products, the PHSA emphasizes the importance of manufacturing control for products whose attributes cannot be precisely defined. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other requirements, the sponsor must develop methods for testing the identity, strength, quality, potency and purity of the final biologic product. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the biologic product candidate does not undergo unacceptable deterioration over its shelf life.\n\nFor a product candidate that is also a human cellular or tissue product, the FDA also requires compliance with current Good Tissue Practices, or cGTPs. These are FDA and EU regulations that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues and cellular and tissue-based products, or HCT/Ps, which are human cells or tissue intended for implantation, transplant, infusion, or transfer into a human recipient. The primary intent of the GTP requirements is to ensure that cell and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission and spread of communicable disease. FDA and EU regulations also require tissue establishments to register and list their HCT/Ps with the FDA or the competent authorities of the EU Member States and, when applicable, to evaluate donors through screening and testing.\n\n47\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nU.S. Review and Approval Processes\n\nThe results of the preclinical tests and clinical trials, together with detailed information relating to the product’s CMC, and proposed labeling, among other things, are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications.\n\nUnder the Prescription Drug User Fee Act, or PDUFA, as amended, each BLA must be accompanied by a significant user fee. The FDA adjusts the PDUFA user fees on an annual basis. The PDUFA also imposes an annual program fee for approved biologics. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business or for a product indication for orphan diseases.\n\nThe FDA reviews a BLA within 60 days of submission to determine if it is substantially complete before the agency accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In that event, the BLA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth, substantive review of the BLA.\n\nThe FDA reviews the BLA to determine, among other things, whether the proposed product candidate is safe and effective for its intended use and whether the product candidate is being manufactured in accordance with cGMP to assure and preserve the product candidate’s identity, safety, strength, quality, potency and purity. The FDA may refer applications for novel biologic products or biologic products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. During the product approval process, the FDA also will determine whether a risk evaluation and mitigation strategy, or REMS, is necessary to assure the safe use of the product candidate. REMS use risk minimization strategies beyond the professional labeling to ensure that the benefits of the product outweigh the potential risks. To determine whether a REMS is needed, the FDA will consider the size of the population likely to use the product, seriousness of the disease, expected benefit of the product, expected duration of treatment, seriousness of known or potential adverse events, and whether the product is a new molecular entity. A REMS could include medication guides, physician communication plans and elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS; the FDA will not approve the BLA without a REMS, if required.\n\nBefore approving a BLA, the FDA will inspect the facilities at which the product candidate is manufactured. The FDA will not approve the product candidate unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product candidate within required specifications. Additionally, before approving a BLA, the FDA typically will inspect one or more clinical sites to assure that the clinical trials were conducted in compliance with IND trial requirements and GCP requirements.\n\nOn the basis of the BLA and accompanying information, including the results of the inspection of the manufacturing facilities, the FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the biologic product with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the BLA, the FDA will issue an approval letter.\n\nIf a product candidate receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited. Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling. The FDA may impose restrictions and conditions on product distribution, prescribing or dispensing in the form of a REMS, or otherwise limit the scope of any approval. In addition, the FDA may require post-marketing clinical trials, sometimes referred to as Phase 4 clinical trials, designed to further assess a biologic product’s safety and effectiveness, and testing and surveillance programs to monitor the safety of approved products that have been commercialized.\n\nThe FDA has agreed to specified performance goals in the review of BLAs under the PDUFA. One such goal is to review standard BLAs in ten months after the FDA accepts the BLA for filing, and priority BLAs in six months, whereupon a review decision is to be made. The FDA does not always meet its PDUFA goal dates for standard and priority BLAs and its review goals are subject to change from time to time. The review process and the PDUFA goal date may be extended by three months if the FDA requests or the BLA sponsor otherwise provides additional information or clarification regarding information already provided in the submission within the last three months before the PDUFA goal date.\n\n48\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nEU Review and Approval Process\n\nIn the EU, medicinal products can only be commercialized after a related MA has been granted. To obtain an MA for a product in the European Economic Area, or EEA (which is comprised of the 27 Member States of the EU plus Norway, Iceland and Liechtenstein), an applicant must submit an MAA, either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EU Member States (decentralized procedure, national procedure or mutual recognition procedure). An MA may be granted only to an applicant established in the EU.\n\nThe centralized procedure provides for the grant of a single MA by the European Commission that is valid for all EU Member States. Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) ATMPs and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, autoimmune and other immune dysfunctions and viral diseases. For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative or for which a centralized process is in the interest of patients, authorization through the centralized procedure is optional on related approval.\n\nUnder the centralized procedure, the EMA’s Committee for Medicinal Products for Human Use, or CHMP, conducts the initial assessment of a product. The CHMP is also responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing MA. The maximum timeframe for the evaluation of an MAA is 210 days, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP. Accelerated assessment may be granted by the CHMP in exceptional cases. If the CHMP accepts a request for accelerated assessment, the time limit of 210 days will be reduced to 150 days (excluding clock stops). The CHMP can, however, revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.\n\nUnlike the centralized authorization procedure, the decentralized MA procedure requires a separate application to, and leads to separate approval by, the competent authorities of each EU Member State in which the product is to be marketed. This application is identical to the application that would be submitted to the EMA for authorization through the centralized procedure. The reference EU Member State prepares a draft assessment and drafts of the related materials within 120 days after receipt of a valid application. The resulting assessment report is submitted to the concerned EU Member States that, within 90 days of receipt, must decide whether to approve the assessment report and related materials. If a concerned EU Member State cannot approve the assessment report and related materials due to concerns relating to a potential serious risk to public health, disputed elements may be referred to the Heads of Medicines Agencies’ Coordination Group for Mutual Recognition and Decentralised Procedures – Human for review. The subsequent decision of the European Commission is binding on all EU Member States.\n\nThe mutual recognition procedure allows companies that have a medicinal product already authorized in one EU Member State to apply for this authorization to be recognized by the competent authorities in other EU Member States. Like the decentralized procedure, the mutual recognition procedure is based on the acceptance by the competent authorities of the EU Member States of the MA of a medicinal product by the competent authorities of other EU Member States. The holder of a national MA may submit an application to the competent authority of an EU Member State requesting that this authority recognize the MA delivered by the competent authority of another EU Member State.\n\nAn MA has, in principle, an initial validity of five years. The MA may be renewed after five years on the basis of a reevaluation of the risk-benefit balance by the EMA or by the competent authority of the EU Member State in which the original MA was granted. To support the application, the MA holder must provide the EMA or the competent authority with a consolidated version of the electronic Common Technical Document providing up-to-date data concerning the quality, safety and efficacy of the product, including all variations introduced since the MA was granted, at least nine months before the MA ceases to be valid. The European Commission or the competent authorities of the EU Member States may decide on justified grounds relating to pharmacovigilance to proceed with one further five-year renewal period for the MA. Once subsequently definitively renewed, the MA shall be valid for an unlimited period. Any authorization which is not followed by the actual placing of the medicinal product on the EU market (for a centralized MA) or on the market of the authorizing EU Member State (for a decentralized MA) within three years after authorization ceases to be valid (the so-called sunset clause).\n\nInnovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as PRIME designation. Products eligible for PRIME must target conditions for which there is an unmet medical need and demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones. Benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements and potentially accelerated MAA assessment once a dossier has been submitted.\n\n49\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nIn the EU, a “conditional” MA may be granted in cases where all the required safety and efficacy data are not yet available. The European Commission may grant a conditional MA for a medicinal product if it is demonstrated that all of the following criteria are met: (i) the benefit-risk balance of the medicinal product is positive, (ii) it is likely that the applicant will be able to provide comprehensive data post-authorization, (iii) the medicinal product fulfils an unmet medical need and (iv) the benefit of the immediate availability to patients of the medicinal product is greater than the risk inherent in the fact that additional data are still required. The conditional MA is subject to conditions to be fulfilled for generating the missing data or ensuring increased safety measures. It is valid for one year and must be renewed annually until all related conditions have been fulfilled. Once any pending studies are provided, the conditional MA can be converted into a traditional MA. However, if the conditions are not fulfilled within the timeframe set by the EMA and approved by the European Commission, the MA will cease to be renewed.\n\nAn MA may also be granted “under exceptional circumstances” where the applicant can show that it is unable to provide comprehensive data on efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced. These circumstances may arise in particular when the intended indications are very rare and, in the state of scientific knowledge at that time, it is not possible to provide comprehensive information, or when generating data may be contrary to generally accepted ethical principles. Like a conditional MA, an MA granted in exceptional circumstances is reserved to medicinal products intended to be authorized for treatment of rare diseases or unmet medical needs for which the applicant does not hold a complete data set that is required for the grant of a standard MA. However, unlike the conditional MA, an applicant for authorization in exceptional circumstances is not subsequently required to provide the missing data. Although the MA “under exceptional circumstances” is granted definitively, the risk-benefit balance of the medicinal product is reviewed annually, and the MA will be withdrawn if the risk-benefit ratio is no longer favorable.\n\nManufacturing Regulations in the EU\n\nVarious requirements apply to the manufacturing and placing on the EU market of medicinal products. The manufacturing of medicinal products in the EU requires a manufacturing authorization, and import of medicinal products into the EU requires a manufacturing authorization allowing for import. The manufacturing authorization holder must comply with various requirements set out in the applicable EU laws, regulations and guidance, including EU cGMP standards. Similarly, the distribution of medicinal products within the EU is subject to compliance with the applicable EU laws, regulations and guidelines, including the requirement to hold appropriate authorizations for distribution granted by the competent authorities of EU Member States. Marketing authorization holders and/or manufacturing and import authorization, or MA holders and/or distribution authorization holders may be subject to civil, criminal or administrative sanctions, including suspension of manufacturing authorization, in case of non-compliance with the EU or EU Member States’ requirements applicable to the manufacturing of medicinal products.\n\nPost-approval Requirements\n\nRigorous and extensive FDA and EU regulation of biologic products continues after approval, particularly with respect to cGMP requirements. Manufacturers are required to comply with applicable requirements in the cGMP regulations, including quality control and quality assurance and maintenance of records and documentation. Other post-approval requirements applicable to biologic products include reporting of cGMP deviations that may affect the identity, potency, purity and overall safety of a distributed product, record-keeping requirements, reporting of adverse effects, reporting updated safety and efficacy information and complying with electronic record and signature requirements. After a BLA is approved, the product also may be subject to official lot release. If the product is subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA, together with a release protocol, showing a summary of the history of manufacture of the lot and the results of all tests performed on the lot. The FDA also may perform certain confirmatory tests on lots of some products before releasing the lots for distribution. In addition, the FDA conducts laboratory research related to the regulatory standards on the safety, purity, potency and effectiveness of biologic products. Failure to comply with the FDA’s post-approval regulations can result in withdrawal of product approval and licensure.\n\nA sponsor also must comply with the FDA’s or EU and/or the applicable EU Member States’ laws and requirements governing advertising and promotion requirements, such as the prohibition on promoting products for uses or in patient populations that are not described in the product’s approved labeling (or Summary of Product Characteristics in the EU) (known as “off-label use”). Discovery of previously unknown problems or the failure to comply with the applicable regulatory requirements may result in restrictions on the marketing of a product or withdrawal of the product from the market as well as possible civil or criminal sanctions. In addition, changes to the manufacturing process or facility generally require prior approval by the FDA or competent foreign regulatory authority before being implemented and other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further review and approval.\n\n50\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nOrphan and RMAT Designation; Accelerated Approval\n\nProducts that are intended for treating rare conditions that affect fewer than 200,000 people in the United States, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug, may qualify for orphan designation. In the EU, a medicinal product can be designated as an orphan medicinal product by the European Commission if the product sponsor can establish that: (i) the product is intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions; (ii) either (a) such conditions affect not more than five in 10,000 persons in the EU when the application is made, or (b) the product without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the necessary investment in developing the medicinal product; and (iii) there exists no satisfactory authorized method of diagnosis, prevention or treatment of the condition that has been authorized in the EU, or even if such method exists, the product will be of significant benefit to those affected by that condition.\n\nOnce marketing authorization has been granted in relation to a medicinal product with orphan designation, the product can benefit from a market exclusivity period in respect of the specific orphan indication for which the drug has been approved for a period of seven years in the United States and for up to ten years in the EU. If the manufacturer is no longer able to assert that the product meets the orphan designation criteria or is not able to supply sufficient quantities of the product, it may lose orphan market exclusivity. In the EU, the period of market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria on the basis of which it received orphan medicinal product destination, including where it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold. Additionally, an MA may be granted to a similar medicinal product with the same orphan indication during the ten year period if: (i) if the applicant consents to a second original orphan medicinal product application, (ii) if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities; or (iii) if the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior to the original orphan medicinal product. A company may voluntarily remove a product from the register of orphan products.\n\nRMAT designation is intended to expedite review of a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, intended to treat, modify, reverse, or cure a serious or life‑threatening disease or condition and for which preliminary clinical evidence indicates the potential to address unmet medical needs for such a disease or condition.\n\nRMAT designation provides potential benefits that include more frequent meetings with the FDA to discuss the development plan for the product candidate, and eligibility for rolling review and priority review of the related BLA. However, RMAT designation does not change the FDA’s standards for product approval. Additionally, RMAT designation can be revoked if the criteria for eligibility cease to be met as clinical data emerges.\n\nAccelerated Approval may be granted for products that are intended to treat a serious or life-threatening condition and that provide a meaningful therapeutic advantage to patients over existing treatments. A product eligible for Accelerated Approval may be approved on the basis of either a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. In clinical trials, a surrogate endpoint is a measurement of laboratory or clinical signs of a disease or condition that substitutes for a direct measurement of how a patient feels, functions or survives. The Accelerated Approval pathway may be contingent on a sponsor’s agreement to complete ongoing longer term studies or conduct additional post-approval confirmatory studies to verify and describe the product’s clinical benefit, and upon submission of such data satisfying the contingency, the BLA is given full approval. Confirmatory data must be provided with due diligence. Failure to confirm a clinical benefit would allow the FDA to withdraw the product from the market on an expedited basis. All promotional materials for products that receive Accelerated Approval are subject to prior review by the FDA.\n\nClinical Trial Data Disclosure\n\nMany jurisdictions have mandatory clinical trial information obligations incumbent on sponsors. In the EU, transparency requirements relating to clinical trial information are established in the CTR, which establishes a general principle according to which information contained in CTIS shall be made publicly accessible unless confidentiality is justified on grounds of protecting personal data or commercially confidential information, protecting confidential communications between EU Member States in relation to the preparation of an assessment report or ensuring effective supervision of the conduct of a clinical trial by EU Member States. This confidentiality exception may be overruled if there is an overriding public interest in disclosure. The publication of data and documents in relation to the conduct of a clinical trial depends on the type of clinical trial and will take place in accordance with specific timelines. The timelines are established by the EMA and are determined based on the documents and the categorization of the clinical trial.\n\n51\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nIn addition, Regulation No. 1049/2001 on access to documents, or the ATD Regulation, and the related EMA policy 0043 on access to documents provide for a wide right for EU-based interested parties to submit an access to documents request to the EMA to access certain information held by the EMA. Only very limited information is exempted from disclosure (i.e., commercially confidential information, which is construed increasingly narrowly, and protected personal data). It is possible for competitors to access and use this data in their own research and development programs anywhere in the world, once these data are in the public domain.\n\nRegulation of Our Operations\n\nAlthough we currently do not have any products on the market, we may be subject to healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which we conduct our business. Such laws may include, without limitation:\n\n•the federal healthcare Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid;\n\n•federal civil and criminal false claims laws, including the federal False Claims Act, and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, to the federal government, including the Medicare and Medicaid programs, claims for payment or approval that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;\n\n•the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program and also created federal criminal laws that prohibit, among other things, knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statements in connection with the delivery of or payment for healthcare benefits, items or services;\n\n•HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and their implementing regulations, which impose obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information held by certain healthcare providers, health plans and healthcare clearinghouses, known as covered entities, and individuals and entities that perform services for them that involve individually identifiable health information, known as business associates as well as covered subcontractors;\n\n•the federal Physician Payments Sunshine Act created under the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively, the ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare and Medicaid Services, or CMS, information related to payments and other transfers of value to physicians (currently defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members;\n\n•analogous state and foreign laws and regulations, such as state and foreign anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers; some state and foreign laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the government, require drug manufacturers to report information related to payments and other transfers of value to other healthcare providers and healthcare entities, marketing expenditures; or drug pricing; and/or ensure the registration of sales personnel; and\n\n•state and foreign laws govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.\n\nIf our operations are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to significant penalties, including, without limitation, administrative, civil and criminal penalties, damages, fines, disgorgement, the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs, imprisonment, suspension or withdrawal of our marketing and commercialization in respect of our commercially approved products, and additional reporting requirements and oversight if we become subject to a corporate\n\n52\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nintegrity agreement or similar agreement to resolve allegations of non-compliance with these laws, any of which could adversely affect our ability to operate our business and our financial results. Responding to investigations can be time-and resource-consuming and can divert management’s attention from the business. Any such investigation or settlement could increase our costs or otherwise have an adverse effect on our business.\n\nHealthcare Reform\n\nThe U.S. and some foreign jurisdictions are considering enacting or have enacted a number of additional legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell our product candidates profitably, if approved. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts, which include major legislative initiatives, such as the ACA, to reduce the cost of care through changes in the healthcare system, including limits on the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical products, especially under government-funded health care programs, and increased governmental control of drug pricing.\n\nThere have been amendments and legal and political challenges to certain aspects of the ACA, as well as efforts to repeal or replace certain aspects of the ACA. For example, on July 4, 2025, the One Big Beautiful Bill Act, or the OBBBA, was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance. The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program. Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies. We expect that additional U.S. federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the U.S. federal government will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.\n\nThe current administration is pursuing policies to reduce regulations and expenditures across government agencies including at U.S. Department of Health and Human Services, or HHS, the FDA, CMS and related agencies. These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business. For example, the current administration has announced agreements with several pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform, U.S. patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues. Other recent actions, for example, include (1) directing agencies to reduce agency workforce and cut programs; (2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products; (3) imposing tariffs on imported pharmaceutical products; and (4) as part of the Make America Healthy Again, or MAHA, Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising. Additionally, the current administration recently called on Congress to enact \"The Great Healthcare Plan,\" to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager, or PBM, payment methodologies, among other things. These actions and policies may significantly reduce U.S. drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks. In June 2024, the U.S. Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations. Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program.\n\nAt the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.\n\nIn the United States, the EU and other potentially significant markets for our product candidates, government authorities and third-party payors are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative products and therapies, which has resulted in lower average selling prices. Furthermore, the increased emphasis on managed healthcare in the United States and on country and regional pricing and reimbursement controls in the EU will put additional pressure on product pricing, reimbursement and usage, which may adversely affect our future product sales and results of operations. These pressures can arise from rules and practices of managed care groups, judicial\n\n53\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\ndecisions and governmental laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical reimbursement policies and pricing in general.\n\nPricing, Coverage and Reimbursement\n\nPricing and reimbursement of a therapeutic product will largely determine the affordability of the product, and whether the product is prescribed and supplied to patients and private insurance companies may take into account government reimbursement methodologies. Due to these proposed and enacted laws, as well as other actions, significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval, particularly for novel products. In both domestic and foreign markets, sales and reimbursement of any approved products will depend, in part, on the extent to which third-party payors, such as government health programs, commercial insurance and managed healthcare organizations provide coverage, and establish adequate reimbursement levels, for such products. Third-party payors are increasingly challenging the prices charged for medical products and services and imposing controls to manage costs. Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the FDA-approved products for a particular indication. Additionally, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. If third-party payors do not consider our products to be cost-effective compared to other therapies, these payors may not cover our products after approved as a benefit under their plans or, if they do, the level of reimbursement may not be sufficient to allow us to sell our products on a profitable basis. Further, coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. Further, the HHS imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis. HHS has also been empowered to negotiate the price of certain single-source biologics that have been on the market for at least 11 years covered under Medicare as part of the Medicare Drug Price Negotiation Program. Each year up to 20 products will be selected by HHS for the Medicare Drug Price Negotiation Program. Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.\n\nIn the EU, pricing and reimbursement schemes vary widely from country to country. The EU provides options for its Member States to restrict the range of products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. EU Member States may approve a specific price for a product, or they may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market. Other EU Member States allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions. Recently, many countries in the EU have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures. Some countries may also require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies (so called health technology assessments) in order to obtain reimbursement or pricing approval. The Health Technology Assessment, or HTA, process is the procedure according to which the assessment of the public health impact, therapeutic impact and the economic and societal impact of use of a given medicinal product in the national healthcare systems of the individual country is conducted. The outcome of HTA regarding specific medicinal products will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU Member States. In December 2021, Regulation No 2021/2282 on HTA Regulation, was adopted in the EU. The HTA Regulation is intended to boost cooperation among Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at level of the EU for joint clinical assessments in these areas. The HTA Regulation has applied from January 12, 2025 although it will enter into force iteratively and initially apply to new active substances to treat cancer and to all ATMPs, it will then be expanded to orphan medicinal products in January 2028, and to all centrally authorized medicinal products as of 2030. Selected high-risk medical devices will also be assessed under the HTA Regulation as of 2026. The HTA Regulation is intended to harmonize the clinical benefit assessment of HTA across the EU. Pricing and reimbursement decisions, based on these assessments, remain the responsibility of individual Member States. See “Risk Factors—Even if we are able to commercialize any approved products, such products may not receive coverage and adequate reimbursement from third-party payors in the United States and in other countries in which we seek to commercialize them, which could harm our business.”\n\nEnvironmental Regulation\n\nU.S. federal and state laws regarding safe working conditions, environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business. These and other laws govern our use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated by, our operations. We may incur significant costs to comply with such laws and regulations now or in the future. If our operations result in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages and governmental fines. We believe that we are in material compliance with applicable environmental laws and regulations that continued compliance therewith will not have a material\n\n54\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\neffect on our business. We cannot predict, however, how changes in these laws and regulations may affect our future operations.\n\nPrivacy and Cybersecurity Regulation\n\nWe are, or may become, subject to numerous privacy and data security laws and regulations in the United States and in other foreign jurisdictions, including, as applicable, the Federal Trade Commission Act, the EU General Data Protection Regulation, or EU GDPR, the EU GDPR as it forms part of the United Kingdom’s law by virtue of Section 3 of the European Union (Withdrawal) Act 2018, as amended, or U.K. GDPR, and the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020, or collectively the CCPA.\n\nThe collection, use, disclosure, transfer or other processing of personal data regarding individuals in the EEA and U.K., including personal health data, is subject to the EU GDPR, and U.K. GDPR, or collectively the GDPR, as applicable. The GDPR, which is wide-ranging in scope, imposes several requirements on us relating to, among other things, the control over personal data by individuals to whom the personal data relates, notice we must provide to individuals regarding our processing of their personal data, the documentation we must maintain, the security and confidentiality of the personal data, data breach notification, and the use of third-party processors in connection with the processing of personal data. The GDPR also imposes strict rules on the transfer of personal data to countries that the European Commission does not consider to provide an adequate level of privacy and data security (including the United States). The GDPR authorizes the imposition of large penalties and other corrective actions for noncompliance, including potential fines of up to €20 million (£17.5 million) or 4% of the annual global revenue of the noncompliant company, whichever is greater, temporary or definitive bans on data processing and other corrective actions or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests. The GDPR requirements related to international data transfers apply not only to third-party transactions, but also to transfers of information between us and our subsidiaries such as Sangamo France, including employee information. The GDPR has increased our responsibility and potential liability in relation to personal data that we process, particularly in light of our acquisition of Sangamo France, and we may be required to put in place additional mechanisms to ensure compliance with the GDPR, which could divert management’s attention and increase our cost of doing business.\n\nIn the EU, the Network and Information Security Directive, or NIS2, which entered into force in January 2023, aims to improve the resilience and incident response capabilities of entities operating in a number of sectors, including the health sector. Non-compliance with NIS2 may result in administrative fines of a maximum of €10 million or up to 2% of the total worldwide turnover of the preceding financial year.\n\nIn the United States, federal, state and local governments have enacted numerous privacy and data security laws, including laws on data breach notification, personal data privacy and consumer protection. For example, the CCPA applies to personal data of consumers, business representatives and employees who are California residents and requires businesses to provide detailed disclosures in privacy notices and honor requests of California residents to exercise certain privacy rights related to their personal data. The CCPA provides for fines and allows private litigants affected by certain data breaches to recover significant statutory damages. Although the CCPA (like other U.S. comprehensive privacy laws) exempts some data processed in the context of clinical trials, the CCPA may increase compliance efforts and costs and potential liability with respect to other personal data we or the third parties we rely on may maintain about California residents. Similar laws have been enacted or proposed by several other states, as well as at the federal and local levels, and expect more states to pass similar laws in the future. These laws may further complicate compliance efforts, and may increase legal risk and compliance costs for us and the third parties upon whom we rely.\n\nCompliance with these and any other applicable privacy and data security laws and regulations is a rigorous and time-intensive process, and we may be required to put in place additional mechanisms ensuring compliance with the new data protection rules. If we fail to comply with any such laws or regulations, we may face significant fines and penalties that could adversely affect our business, financial condition and results of operations. Furthermore, the laws are not consistent, and compliance in the event of a widespread data breach is costly. See “Risk Factors—Our current and future relationships with healthcare providers, customers and third-party payors subject us to applicable anti-kickback, fraud and abuse, privacy, data security and other healthcare laws and regulations. If we fail to comply with such regulations, we could face regulatory investigations or actions, litigation (including class claims) and mass arbitration demands, and substantial fines and penalties, and our business, reputation, results of operations, financial condition and prospects could be adversely affected.”\n\nHUMAN CAPITAL MANAGEMENT\n\nOur Mission and Our Employees\n\nAt Sangamo, we are committed to translating ground-breaking science into genomic medicines that transform patients’ lives. We are a passionate group of biotechnology professionals with years of experience and technical expertise, committed to\n\n55\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\ndeveloping best-in-class genomic medicines. We embrace collaboration, discipline and efficiency while welcoming fresh ideas and stimulating personal development. We encourage and embrace an inclusive culture and believe it enhances our work towards one common goal: to transform the lives of the patients we aim to serve.\n\nWe view our employees as one of our most valuable assets in serving our mission. We compete in the highly competitive biotechnology industry, and attracting, retaining and developing a diverse group of talented employees is crucial to our strategy and our ability to compete effectively. We are committed to the development and retention of our workforce. There continues to be a shortage of skilled individuals with substantial experience discovering, developing and manufacturing genomic medicines, which is likely to continue. As a result, there continues to be competition between biopharmaceutical companies and academic institutions for individuals with these skills.\n\nOur Values\n\nWe believe success comes when we align our core values with our mission to deliver genomic medicines that replace today’s symptomatic treatments and transform patients’ lives. Our core values are:\n\n•Doing what’s right for patients:\n\n◦We collaborate with purpose and are driven by results that benefit patients.\n\n◦We strive to put patient safety and quality of care first.\n\n◦Patient needs drive our sense of urgency to deliver medicines.\n\n◦We embrace our responsibility to pioneer the field of genomic medicine bioethically.\n\n◦We take an inclusive approach to guide our development efforts.\n\n•Succeeding through teamwork:\n\n◦We are driven by our shared vision that genomic medicine will transform the lives of patients and the field of healthcare.\n\n◦We are a passionate and dedicated group of individuals who collaborate proactively and openly to execute and progress our business forward.\n\n◦We define our priorities clearly, communicate them and take collective accountability to deliver results for all stakeholders.\n\n◦We are resilient and determined to succeed together because patients are depending on us.\n\n•Innovating through smart decisions:\n\n◦We courageously, relentlessly, and urgently pursue the journey of innovation to succeed in the field of genomic medicine.\n\n◦We mine scientific possibilities with the goal of unlocking new treatment solutions for serious diseases.\n\n◦We strive to achieve our business goals through agile, inclusive and efficient decision making.\n\n◦We learn and grow from decades of scientific experience to develop therapies at the cutting edge of medicine.\n\n◦We learn from failure, and seek to continuously improve performance, as part of the journey to achieve breakthroughs.\n\n•Fostering belonging:\n\n◦We develop shared goals that create a sense of belonging.\n\n◦We are a company where individuals from all backgrounds can flourish, grow and develop their expertise while bringing their authentic selves to work.\n\n◦We feel connected to our local communities, the environment in which we live and the patient communities we serve.\n\n◦We come together to understand our scientific learnings and progress the evolution of our business.\n\n◦We are committed to nurturing diverse and inclusive environments to advance healthcare equity.\n\n56\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nOur Management of Human Capital\n\nOur human resource function focuses on the attraction and recruitment of candidates, leadership training and development, total rewards packages consisting of compensation and benefits, and employee engagement and retention. As of March 27, 2026, our global human resource function comprised four full time human resource professionals.\n\nAs of March 27, 2026, we had 142 full time employees located in the United States and the United Kingdom. Of these employees, 140 were located in the United States, primarily in the San Francisco Bay Area, and the remaining two were located in the United Kingdom.\n\nOf the 142 full time employees, 57 were primarily engaged in research and development activities, 43 were primarily engaged in technical operations and manufacturing and 42 were primarily engaged in general and administrative activities. We also engage the services of independent contractors and consultants as needed for special or temporary projects or specific expertise.\n\nTo manage our human resources, we track and report internally on key talent metrics including headcount by business unit and country, historical headcount growth, turnover, new hires and terminations, open roles and employee demographics including gender, race and ethnicity. Our senior executives use these metrics to assist with resource planning, recruitment and retention initiatives and the design of our compensation and benefits programs. We share these metrics quarterly with the Compensation Committee of our Board of Directors to assist it in fulfilling its duties to establish our enterprise compensation philosophy, administer our compensation and benefit plans, evaluate the performance of our executive officers and key employees and review and monitor management development and succession plans.\n\nOur leaders work closely with managers and employees to understand and shape our culture and work dynamics to identify areas of focus that will increase overall employee engagement.\n\nThe following graphs represent the composition of employees at Sangamo as of March 27, 2026:\n\n57\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\n58\n\n[Table of Contents](#i29aeb4416f69482f8f7bc32e0d48731a_7)\n\nOur Compensation and Benefits\n\nGiven the highly competitive nature of our industry and the importance of recruitment and retention to our success, we strive to provide our employees with what we believe is a very competitive and comprehensive total rewards package of compensation, benefits and development opportunities. This package includes at or above-market pay; healthcare benefits for employees and family members; a health savings account for eligible U.S. employees with above market employer contributions; generous paid time off benefits; family leave; bereavement leave; flexible work schedules; contributions to retirement and/or pension plans; a supplemental long term disability plan; mental health benefits and onsite gym access. In addition, we offer a monthly stipend for employees to spend on health and well-being. We also offer every full-time employee globally the benefit of equity ownership in Sangamo through stock option grants and/or restricted stock units. Our U.S. employees are also eligible to participate in an employee stock purchase plan, which offers the opportunity to purchase our common stock at a discount of at least 15%.\n\nProperties\n\nSangamo is headquartered in Richmond, California, and has an additional facility in Brisbane, California.\n\nTrademarks and Tradenames\n\nSANGAMO THERAPEUTICS and SANGAMO THERAPEUTICS Design are registered trademarks in Australia, Canada, the European Union, Japan, the United Kingdom and the United States. The trademarks UNIVERSAL GENE RECOGNITION, UNIVERSAL GENETOOLS and ZFP THERAPEUTIC are registered in Canada. An intent-to-use application is pending regarding the trademark GEXREV in the United States. All other trademarks or trade names referred to in this Annual Report on Form 10-K are the property of their respective owners.\n\nCompany Information\n\nWe were incorporated in June 1995 in the state of Delaware and in January 2017, we changed our name from “Sangamo BioSciences, Inc.” to “Sangamo Therapeutics, Inc.” Our principal executive offices are located at 501 Canal Blvd., Richmond, California 94804. Our telephone number is (510) 970-6000.\n\nAvailable Information\n\nOur website is located at www.sangamo.com. This Annual Report on Form 10-K, our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act are available free of charge on our website as soon as reasonably practicable after we electronically file this material with, or furnish it to, the Securities and Exchange Commission, or SEC. Information found on, or accessible through, our website is not a part of, and is not incorporated into, this Annual Report on Form 10-K. In addition, the SEC maintains a website at www.sec.gov that contains reports, proxy and information statements and other information regarding issuers that file electronically with the SEC."}