Prion Diseases

Novel AAV capsid engineered by Sangamo showed robust penetration of blood-brain barrier (BBB) and widespread transgene expression throughout brain in non-human primates (NHPs) following intravenous administration. Demonstrated industry-leading brain tropism and enrichment in NHPs, resulting in 700-fold higher transgene expression than benchmark capsid AAV9. Capsid-enabled delivery of zinc finger payloads targeting prion disease and tauopathies resulted in robust and widespread repression of target genes. STAC-BBB capsid could potentially unlock multiple neurology epigenetic regulation programs paused by Sangamo pending identification of suitable capsid and could be advanced either internally or with a collaborator. Sangamo expects to to three neurology Investigational New Drug (IND) submissions and/or Clinical Trial Applications (CTA) by end of 2025. Sangamo to discuss results in conference call scheduled for Wednesday, March 13 at 4:30pm Eastern Time. RICHMOND, Calif.--(BUSINESS WIRE)-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced preclinical data from its proprietary adeno-associated virus (AAV) capsid variant, STAC-BBB, that demonstrated robust penetration of the blood-brain barrier (BBB) and strong transgene expression throughout the central nervous system (CNS) of NHPs when administered intravenously at clinically-relevant doses, outperforming results obtained by Sangamo for other known neurotropic capsid variants evaluated in the study. Importantly, potent repression of target genes was observed in brain cells expressing the zinc finger cargo, indicating that STAC-BBB could enable development of genomic medicines to potentially treat a wide range of neurological diseases. “The advancement of neurological medicines has long been limited by the inability to achieve widespread CNS delivery, an essential attribute for an effective treatment for devastating neurological disorders. We are extremely encouraged that STAC-BBB, a potentially game-changing capsid variant engineered using our SIFTER capsid platform, demonstrated results that outperformed other known neurotropic capsid variants, achieving widespread brain delivery and transgene expression, desired de-targeting of liver and other peripheral tissues and a favorable safety profile,” said Sandy Macrae, Chief Executive Officer of Sangamo. “Furthermore, these data demonstrated that delivery of our zinc finger epigenetic regulators using STAC-BBB could result in a meaningful repression of disease-relevant target genes throughout the brain, which we believe may result in profound improvements in disease pathology and progression. These data further support our transformation into a neurology-focused genomic medicine company focused on combining potent epigenetic regulation capabilities with innovative capsid delivery technology to develop best-in-class neurology medicines.” Sangamo intends to use the novel STAC-BBB capsid in its wholly owned prion disease and tauopathy programs. In addition, STAC-BBB could potentially unlock multiple neurology epigenetic regulation programs that were paused by Sangamo pending the identification of a suitable capsid, including programs previously in development under Sangamo’s former collaboration agreements with Biogen and Novartis. Sangamo is exploring avenues to resume development of these programs internally, subject to receipt of adequate funding, or with new potential collaborators. Summary of STAC-BBB Preclinical Data In NHP studies when administered intravenously at clinically relevant doses, STAC-BBB demonstrated its potential to be a leading neurotropic capsid. Highlights include: Broad brain coverage. Robust penetration of the BBB and widespread transgene expression throughout the brain, including key regions integral to human neurological diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease and prion disease. Industry-leading brain tropism. Exhibited 700-fold higher transgene expression in neurons compared to the benchmark capsid AAV9 and outperformed all other known published neurotropic capsid variants evaluated in the study. Widespread neuronal transduction across all animals. STAC-BBB mediated robust expression of zinc finger cargo in neurons, the key cell type to target for treatment of neurological diseases. Moreover, results were dose-dependent and consistent across all NHPs in the study. Potent and widespread repression of target genes. Capsid-enabled delivery of zinc finger payloads resulted in the repression of prion and tau genes across key brain regions, demonstrating the potential for modification of disease progression in prion disease and various tauopathies. Visualization of gene expression in individual brain cells by RNAscope revealed highly potent repression of tau in neurons expressing the zinc finger cargo across multiple brain regions. Desired de-targeting of the liver and other peripheral organs. Capsid biodistribution was shown to be enriched in the CNS and de-targeted from the liver, dorsal root ganglia (DRG) and other peripheral organs. This biodistribution pro by STAC-BBB is optimal for an AAV-based treatment of neurological diseases. Favorable safety profile. STAC-BBB was well tolerated in NHPs, with no notable treatment related pathological findings in brain, spinal cord or peripheral tissues. Manufacturable using standard processes and at scale. 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. Sangamo expects to IND submission for its Nav1.7 program addressing chronic neuropathic pain, which leverages an intrathecally administered capsid, in the fourth quarter of 2024, and a CTA submission for its prion disease program, which is expected to leverage the STAC-BBB capsid, in the fourth quarter of 2025, each subject to additional funding. Sangamo also intends to resume development of its tau program leveraging the STAC-BBB capsid, with an IND submission expected as early as the fourth quarter of 2025. The Sangamo management team will discuss these results on a conference call on Wednesday, March 13 at 4:30pm Eastern Time. Participants should register for, and access, the call using this link. While not required, it is recommended you join 10 minutes prior to the event start. Once registered, participants will be given the option to either dial into the call with the number and unique passcode provided or to use the dial-out option to connect their phone instantly. An updated corporate presentation is available in the Investors and Media section under Presentations. The link to access the live webcast can also be found on the Sangamo website in the Investors and Media section under Events. A replay will be available following the conference call, accessible at the same link. About Sangamo Therapeutics Sangamo Therapeutics is a genomic medicine company dedicated to translating ground-breaking science into medicines that transform the lives of patients and families afflicted with serious neurological diseases who do not have adequate or any treatment options. Sangamo’s zinc finger epigenetic regulators are ideally suited to potentially address devastating neurological disorders and Sangamo’s capsid discovery platform is expanding delivery beyond currently available intrathecal delivery capsids, including in the central nervous system. Sangamo’s pipeline also includes multiple partnered programs and programs with opportunities for partnership and investment. To learn more, visit and connect with us on LinkedIn and Twitter/X. Forward-Looking Statements This press release contains forward-looking statements regarding our current expectations. These forward-looking statements include, without limitation, statements relating to: expectations regarding the therapeutic potential of Sangamo’s technologies, including the delivery of zinc finger epigenetic regulators using STAC-BBB to result in the repression of disease-relevant target genes in the brain, to result in profound improvements in disease pathology and progression, to modify disease progression in prion disease and various tauopathies, to be manufacturable at commercial scale using standard cell culture and purification processes, to be soluble using known excipients, and to be characterized using available analytics; Sangamo’s intentions to use STAC-BBB in two of its epigenetic regulation product candidates under development internally; expectations that preclinical data from STAC-BBB will support Sangamo’s transformation into a neurology-focused genomic medicine company; expectations regarding STAC-BBB’s potential to unlock multiple neurology epigenetic regulation programs that have been paused by Sangamo pending the identification of a suitable capsid, and plans to either resume their development internally, with receipt of additional funding, or with a new potential collaborator; Sangamo’s plans to submissions and/or CTAs and the expected timing of such regulatory submissions; and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to the uncertain and costly research and development process, including the risk that preclinical results may not be indicative of results in any future clinical trials; Sangamo’s lack of capital resources to fully develop, obtain regulatory approval for and commercialize its product candidates, including Sangamo’s ability to secure a partnership or the funding required to initiate planned IND and/or CTA submissions in a timely manner or at all; Sangamo’s need for substantial additional funding to execute its operating plan and to continue to operate as a going concern, including the risk that Sangamo will be unable to obtain the funding necessary to advance Sangamo’s Nav1.7, prion disease and tau programs and to otherwise continue to operate as a going concern, in which case, Sangamo may be required to cease operations entirely, liquidate all or a portion of its assets, and/or or seek protection under applicable bankruptcy laws; the effects of macroeconomic factors or financial challenges, including as a result of the ongoing overseas conflict, current or potential future bank failures, inflation and elevated interest rates, on the global business environment, healthcare systems and business and operations of Sangamo and our collaborators; the research and development process; the potential for technological developments that obviate technologies used by Sangamo; Sangamo’s reliance on collaborators and its potential inability to secure additional collaborations, and Sangamo’s ability to achieve expected future operating results. There can be no assurance that we and our current or potential future collaborators will be able to develop commercially viable products. Actual results may differ materially from those projected in these forward-looking statements due to the risks and uncertainties described above and other risks and uncertainties that exist in the operations and business environments of Sangamo and its collaborators. These risks and uncertainties are described more fully in Sangamo’s Securities and Exchange Commission, or SEC, filings and reports, including in its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC, and future filings and reports that Sangamo makes from time to time with the SEC. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

Data from novel proprietary neurotropic adeno-associated virus (AAV) delivery capsid, STAC-BBB, demonstrated industry-leading blood-brain barrier (BBB) penetration in non-human primates (NHPs) following intravenous administration, with capsid-enabled delivery of zinc finger payloads targeting prion disease and tauopathies resulting in potent and widespread repression of target genes. Chronic neuropathic pain and prion disease preclinical programs advance, with investigational new drug (IND) and clinical trial authorization (CTA) submissions expected in the fourth quarters of 2024 and 2025, respectively. Announced U.S. Food and Drug Administration (FDA) alignment on an abbreviated pathway to potential approval, and grant by European Medicines Agency (EMA) of priority medicines (PRIME) eligibility for isaralgagene civaparvovec in Fabry disease. Pfizer anticipates Biologics License Application (BLA) and marketing authorization application (MAA) submissions for Hemophilia A collaboration by early 2025 if the pivotal readout is supportive. RICHMOND, Calif.--(BUSINESS WIRE)-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, today reported recent business highlights and fourth quarter and full year 2023 financial results, including meaningful data to support advancement of its neurology pipeline. “In 2023, Sangamo announced the prioritization of its pipeline programs that support our focus as a neurology-focused genomic medicine company,” said Sandy Macrae, Chief Executive Officer of Sangamo. “With the meaningful preclinical data announced today, we believe our ability to combine potent zinc finger epigenetic regulation payloads with exciting new industry-leading capsid delivery technology could unlock significant potential for the treatment of devastating neurological diseases, indications for which delivery of treatments to the central nervous system has historically proved challenging. In the near-term, we are also seeking to create value by partnering our Fabry disease program, for which we aligned with the FDA on a potentially abbreviated and more cost-effective timeline and received EMA PRIME eligibility. We look forward to advancing our pipeline into the clinic to develop therapies designed to target neurological diseases with high unmet medical needs.” Recent Business Highlights Prioritized Neurology Pipeline Sangamo is developing epigenetic regulation therapies to treat serious neurological diseases and novel proprietary AAV capsids designed to deliver our therapies to the intended neurological targets, including across the blood-brain barrier. Novel AAV Capsid Delivery Technology – Data demonstrated industry-leading BBB penetration and brain transduction in NHPs, with capsid-enabled delivery of zinc finger payloads targeting prion disease and tauopathies resulting in potent and widespread repression of target genes. Novel STAC-BBB capsid demonstrated robust penetration of BBB with 700-fold higher transgene expression in neurons compared to the benchmark capsid AAV9 and outperformed all other known published capsid variants evaluated in the study. STAC-BBB mediated robust expression of zinc finger cargo in neurons, with potent and widespread repression of prion and tau genes observed across key brain regions, demonstrating the potential for modification of disease progression in prion disease and various tauopathies. Visualization of gene expression in individual brain cells by RNAscope revealed highly potent repression of tau in neurons expressing the zinc finger cargo, across multiple brain regions. Capsid biodistribution pro optimal for the treatment of neurological diseases with AAV-based treatments, highlighted by the observed enrichment in the CNS and de-targeting from the liver, dorsal root ganglia (DRG) and other peripheral organs. STAC-BBB was well tolerated in NHPs, with no notable treatment related pathological findings in brain, spinal cord or peripheral tissues. We believe that 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. Chronic Neuropathic Pain – Preclinical data demonstrated potent and specific repression of Nav1.7 expression without impacting other sodium channels and that zinc finger repressors (ZFRs) were well tolerated in NHPs; IND submission expected in fourth quarter of 2024. IND-enabling toxicology studies are nearing completion. An IND submission is expected in the fourth quarter of 2024. Prion Disease – Preclinical data demonstrated that AAV-delivered ZFRs significantly reduced expression of the prion protein in the brain, extended lifespan and limited formation of toxic prion aggregates in mice; CTA expected in the fourth quarter of 2025. CTA-enabling studies continue to advance. Prion-targeted zinc finger repressor, delivered via an intravenous administration of the STAC-BBB novel capsid, resulted in a dose-dependent repression of prion genes in NHPs. A CTA submission is expected in the fourth quarter of 2025. Tauopathies – Preclinical data demonstrated that AAV-delivered ZFRs significantly reduced expression of tau mRNA in brain of NHPs; intend to resume development of this program, leveraging STAC-BBB; IND submission expected as early as the fourth quarter of 2025. Intend to resume development of our previously paused tau program, leveraging the newly identified STAC-BBB capsid variant, subject to additional funding. Tau clinical-lead zinc finger repressor, delivered via an intravenous administration of the STAC-BBB novel capsid, resulted in a dose-dependent repression of tau genes in NHPs. Visualization of gene expression in individual brain cells by RNAscope revealed highly potent repression of tau in neurons expressing the zinc finger cargo across multiple brain regions. We expect the IND submission could occur as early as the fourth quarter of 2025. Other Programs Fabry Disease – Dosed total of 32 patients in Phase 1/2 STAAR study, with updated clinical data presented at 20th Annual WORLDSymposium showing sustained benefit and differentiated safety pro >; announced FDA alignment on abbreviated pathway to potential approval; actively seeking collaboration partner to advance asset toward potential registration and commercialization. Dosed seven additional patients in the dose expansion phase of the Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, our wholly owned gene therapy product for the treatment of Fabry disease, for a total of 32 patients dosed to date. Presented updated clinical data at the 20th Annual WORLDSymposium in San Diego, CA in February 2024, showing that elevated levels of α-Gal A activity were sustained in all 24 patients evaluated as of the September 19, 2023 data cutoff date and 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. All 13 patients who were withdrawn from Enzyme Replacement Therapy (ERT) remain off ERT as of March 12, 2024. In the 13 patients followed for 12-months or more after treatment, renal function remained stable, and significant improvements in overall disease severity, quality of life, and gastrointestinal symptoms compared to baseline were reported. Aligned with the FDA that data from a single, adequate, and well-controlled study may form the primary basis of approval of a BLA for isaralgagene civaparvovec, enabling a potentially abbreviated and more cost-effective pathway to BLA submission than originally anticipated. The study would enroll up to 25 patients, both male and female, without the need for a control arm. A head-to-head comparison with ERT is not part of the proposed study design deemed acceptable by the FDA. Granted PRIME eligibility from the EMA for isaralgagene civaparvovec, which aims to enhance support for the development of medicines that target an unmet medical need and is intended to optimize development plans and expedite review and approval processes. Granted Innovative Licensing and Access Pathway (ILAP) for isaralgagene civaparvovec from U.K. Medicines and Healthcare products Regulatory Agency (MHRA) which aims to accelerate time to market and facilitate access to medicines. Isaralgagene civaparvovec has already received Orphan Medicinal Product designation from the EMA as well as Orphan Drug, Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA. Completed screening and enrollment in the Phase 1/2 STAAR study and expect to complete dosing of remaining patients in the first half of 2024. Deferring additional investments in planning for a potential registrational trial until a collaboration partnership or financing for this program is secured. Hemophilia A (Pfizer) – Pivotal data read-out in Phase 3 AFFINE trial expected in mid-2024; BLA and MAA submissions anticipated by early 2025 if pivotal readout is supportive. A pivotal readout is expected in mid-2024 in the Phase 3 AFFINE trial of giroctocogene fitelparvovec, an investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A. Pfizer anticipates BLA and MAA submissions by early 2025 if the pivotal readout is supportive. Presented updated data with Pfizer from the Phase 1/2 ALTA study of giroctocogene fitelparvovec in an oral presentation at the 65th American Society for Hematology Annual Meeting and Exposition in December 2023. Eligible to earn from Pfizer up to $220.0 million in milestone payments upon the achievement of certain regulatory and commercial milestones for giroctocogene fitelparvovec and product sales royalties of 14% - 20% if giroctocogene fitelparvovec is approved and commercialized, subject to certain reductions. CAR-Tregs – In alignment with previously announced strategic transformation, announced winddown of the Company’s French research and manufacturing operations and a corresponding reduction in workforce; continuing to seek a potential collaboration partner or external investment in the CAR-Treg cell therapy programs. Announced a winddown of Sangamo’s French operations and a corresponding reduction in workforce, including closure of Sangamo’s cell therapy manufacturing facility and research labs in Valbonne, France, which is expected to commence in April 2024 and be complete by end of year. We expect this restructuring to result in the elimination of all roles in France (approximately 93). Dosed two additional patients in the Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous CAR-Treg cell therapy treating patients receiving an HLA-A2 mismatched kidney from a living donor, including the first patient in the new fourth, highest dose cohort. Expect to dose up to two additional patients in the fourth highest-dose level cohort by the end of the second quarter of 2024. Plan to continue seeking a potential collaboration partner or external investment in our autologous CAR-Treg cell therapy programs. Fourth Quarter and Full Year 2023 Financial Results Consolidated net loss for the fourth quarter ended December 31, 2023 was $60.3 million, or $0.34 per share, compared to a net loss of $52.0 million, or $0.32 per share, for the same period in 2022. For the year ended December 31, 2023, consolidated net loss was $257.8 million, or $1.48 per share, compared to consolidated net loss of $192.3 million, or $1.25 per share, for the year ended December 31, 2022. Revenues Revenues for the fourth quarter ended December 31, 2023 were $2.0 million, compared to $27.2 million for the same period in 2022. The decrease of $25.2 million in revenues was primarily attributed to a decrease of $17.5 million in revenue relating to our collaboration agreement with Kite, reflecting a reduction in level of our research and development services, and a decrease of $10.3 million in revenue relating to our collaboration agreement with Novartis, due to the impact of termination of the collaboration agreement. These decreases were partially offset by an increase of $2.6 million in revenues from other licensing agreements. Revenues were $176.2 million in 2023, compared to $111.3 million in 2022. The increase of $64.9 million in revenues in 2023 compared to 2022, was primarily attributed to an increase of $106.4 million in revenue relating to our collaboration agreement with Biogen, primarily due to the impact of termination of the collaboration agreement in June 2023, which resulted in an increase in the measure of proportional cumulative performance on this collaboration, an increase of $3.8 million in revenue relating to our license agreement with Sigma-Aldrich Corporation, and an increase of $3.6 million in revenues from other licensing agreements. These increases were partially offset by a decrease of $27.5 million in revenue relating to our collaboration agreement with Novartis due to the termination of the collaboration agreement in June 2023, a decrease of $18.1 million in revenue relating to our collaboration agreement with Kite due to a reduction in the estimated future level of our research and development services related to this collaboration, and a decrease of $3.3 million in revenue relating to our collaboration agreement with Sanofi due to the termination of the collaboration agreement in June 2022. GAAP and Non-GAAP Operating Expenses Three Months Ended Year Ended December 31, December 31, (In millions) 2023 2022 2023 2022 Research and development $ 50.7 $ 66.2 $ 234.0 $ 249.9 General and administrative 13.1 16.4 61.2 62.7 Impairment of goodwill and indefinite-lived intangible assets - - 89.5 - Impairment of long-lived assets 0.3 - 65.5 - Total operating expenses 64.1 82.6 450.2 312.6 Impairment of goodwill and indefinite-lived intangible assets - - (89.5 ) - Impairment of long-lived assets (0.3 ) - (65.5 ) - Depreciation and amortization (1.8 ) (3.3 ) (15.1 ) (12.1 ) Stock-based compensation expense (6.1 ) (8.3 ) (27.4 ) (31.7 ) Non-GAAP operating expenses $ 55.9 $ 71.0 $ 252.7 $ 268.8 Total operating expenses on a GAAP basis for the fourth quarter ended December 31, 2023 were $64.1 million compared to $82.6 million for the same period in 2022. Non-GAAP operating expenses, which exclude impairment charges, depreciation and amortization, and stock-based compensation expense, for the fourth quarter ended December 31, 2023 were $55.9 million, compared to $71.0 million for the same period in 2022. The decrease in total operating expenses on a GAAP and non-GAAP basis was primarily attributable to lower compensation and other personnel costs mainly due to a reduction in the bonus expense and lower headcount as a result of restructuring of operations and a corresponding reduction in workforce announced during the year, and a decrease in research and clinical expenses due to deferral and reprioritization of certain programs. These decreases were partially offset by restructuring charges related to the reductions in workforce announced in April and November 2023, and the France restructuring. The expense related to the France restructuring was recorded in the fourth quarter of 2023 as the payouts are based an ongoing post-employment benefit plan, and the payments were probable and could be estimated as of December 31, 2023. Total operating expenses on a GAAP basis in 2023 were $450.2 million compared to $312.6 million in 2022. Non-GAAP operating expenses, which exclude impairment charges, depreciation and amortization, and stock-based compensation expense, were $252.7 million in 2023 compared to $268.8 million in 2022. Operating expenses on a GAAP basis included non-cash charges relating to impairment of goodwill and indefinite-lived intangible assets of $89.5 million, and impairment of long-lived assets of $65.5 million, which were a result of continued decline in our stock price and related market capitalization and termination of our collaboration agreements with Biogen and Novartis. The decrease in total operating expenses on a non-GAAP basis was primarily attributable to a reduction in the bonus expense and lower headcount as a result of restructurings of operations and corresponding reductions in workforce announced during the year, and a decrease in preclinical and clinical expenses due to the termination of collaboration agreements with Biogen and Novartis and deferral and reprioritization of certain programs. These decreases were partially offset by restructuring charges related to the reductions in workforce announced in April and November 2023, and the France restructuring. Cash, Cash Equivalents and Marketable Securities Cash, cash equivalents and marketable securities as of December 31, 2023 were $81.0 million, compared to $307.5 million as of December 31, 2022. During the year ended December 31, 2023, we raised approximately $15.1 million in net proceeds under our at-the-market offering program. We believe that our available cash, cash equivalents and marketable securities as of December 31, 2023, in combination with potential future cost reductions, will be sufficient to fund our planned operations into the third quarter of 2024, excluding any additional capital raised. We are actively pursuing opportunities to raise additional capital. Financial Guidance for 2024 On a GAAP basis, we expect total operating expenses in the range of approximately $145 million to $165 million in 2024, which includes non-cash stock-based compensation expense and depreciation and amortization, subject to additional funding. We expect non-GAAP total operating expenses, excluding estimated non-cash stock-based compensation expense of approximately $13 million, and depreciation and amortization of approximately $7 million, in the range of approximately $125 million to $145 million in 2024, subject to additional funding. Upcoming Events Sangamo plans to participate in the following events: Investor Conferences RBC Capital Markets Global Healthcare Conference, May 14-15, 2024 Jefferies Global Healthcare Conference, June 5-6, 2024 H.C. Wainwright 5th Annual Neuro Perspectives Virtual Conference, June 27, 2024 Access links for available webcasts for these investor conferences will be available on the Sangamo website in the Investors and Media section under Events. Available materials will be found on the Sangamo website after the event under Presentations. Conference Call The Sangamo management team will hold a corporate call to further discuss program advancements and financial updates on Wednesday, March 13 at 4:30pm Eastern Time. Participants should register for, and access, the call using this link. While not required, it is recommended you join 10 minutes prior to the event start. Once registered, participants will be given the option to either dial into the call with the number and unique passcode provided or to use the dial-out option to connect their phone instantly. An updated corporate presentation is available in the Investors and Media section under Presentations. The link to access the live webcast can also be found on the Sangamo website in the Investors and Media section under Events. A replay will be available following the conference call, accessible at the same link. About Sangamo Therapeutics Sangamo Therapeutics is a genomic medicine company dedicated to translating ground-breaking science into medicines that transform the lives of patients and families afflicted with serious neurological diseases who do not have adequate or any treatment options. Sangamo’s zinc finger epigenetic regulators are ideally suited to potentially address devastating neurological disorders and Sangamo’s capsid discovery platform is expanding delivery beyond currently available intrathecal delivery capsids, including in the central nervous system. Sangamo’s pipeline also includes multiple partnered programs and programs with opportunities for partnership and investment. To learn more, visit and connect with us on LinkedIn and Twitter/X. Forward-Looking Statements This press release contains forward-looking statements regarding our current expectations. These forward-looking statements include, without limitation, statements relating to: the therapeutic and commercial potential of Sangamo’s product candidates and its engineered capsids, including the ability of STAC-BBB to unlock potential for the treatment of various neurological diseases, the anticipated plans and timelines of Sangamo and its collaborators dosing patients in and conducting our ongoing and potential future clinical trials and presenting clinical data from our clinical trials, including expectations regarding the conclusion of dosing in our Phase 1/2 STAAR study, plans for patient dosing in the STEADFAST study, the anticipated advancement of Sangamo’s product candidates to late-stage development, including plans to seek a potential partner or additional financing to proceed with potential future Phase 3 trials of isaralgagene civaparvovec and the design and timing thereof, the timeline to present data from the Phase 3 AFFINE trial and to make BLA and MAA submissions for giroctocogene fitelparvovec, the potential to earn milestone payments and receive product sales royalties if giroctocogene fitelparvovec is approved and commercialized, expectations regarding advancement of Sangamo’s preclinical neurology programs, including announcement of data from, and anticipated IND and CTA submissions related to, such programs, plans to seek a partner for or investor in Sangamo’s CAR-Treg program, expectations concerning Sangamo’s announced winddown of our French research and manufacturing operations and a corresponding reduction in workforce and the expected charges and cost savings associated with such restructuring; future potential cost reductions, Sangamo’s expected cash runway, Sangamo’s 2024 financial guidance related to GAAP and non-GAAP total operating expenses, impairments and stock-based compensation, plans to participate in industry and investor conferences, efforts to secure additional funding, and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to Sangamo’s lack of capital resources to fully develop, obtain regulatory approval for and commercialize its product candidates, including the ability to secure the funding or partnerships required to advance its preclinical and clinical programs; Sangamo’s ability to execute its restructurings as currently contemplated; the actual charges associated with the restructurings being higher than anticipated or changes to the assumptions on which the estimated charges associated with the restructurings are based; Sangamo’s ability to achieve projected cost savings in connection with the restructurings and to further reduce operating expenses; unintended consequences from the restructuring that impact Sangamo’s business; Sangamo’s need for substantial additional funding to execute our operating plan and to continue to operate as a going concern, including the risk that Sangamo will be unable to obtain the funding necessary to advance its preclinical and clinical programs and to otherwise operate as a going concern, in which case Sangamo may be required to cease operations entirely, liquidate all or a portion of its assets and/or seek protection under the U.S. Bankruptcy Code; the uncertain and costly research and development process, including the risk that preclinical results may not be indicative of results in any future clinical trials; the effects of macroeconomic factors or financial challenges, including as a result of the ongoing overseas conflict, current or potential future bank failures, inflation and rising interest rates, on the global business environment, healthcare systems and business and operations of Sangamo and its collaborators, including the initiation and operation of clinical trials; the impacts of clinical trial delays, pauses and holds on clinical trial timelines and commercialization of product candidates; the uncertain timing and unpredictable nature of clinical trial results, including the risk that therapeutic effects in the Phase 3 AFFINE trial will not be durable in patients as well as the risk that the therapeutic effects observed in the latest preliminary clinical data from the Phase 1/2 STAAR study will not be durable in patients and that final clinical trial data from the study will not validate the safety and efficacy of isaralgagene civaparvovec, and that the patients withdrawn from ERT will remain off ERT; the unpredictable regulatory approval process for product candidates across multiple regulatory authorities; reliance on results of early clinical trials, which results are not necessarily predictive of future clinical trial results, including the results of any registrational trial of Sangamo’s product candidates; the potential for technological developments that obviate technologies used by Sangamo; Sangamo’s reliance on collaborators and its potential inability to secure additional collaborations, and Sangamo’s ability to achieve expected future operating results. All forward-looking statements about our future plans and expectations, including our financial guidance, are subject to our ability to secure adequate additional funding. There can be no assurance that Sangamo and its collaborators will be able to develop commercially viable products. Actual results may differ materially from those projected in these forward-looking statements due to the risks and uncertainties described above and other risks and uncertainties that exist in the operations and business environments of Sangamo and its collaborators. These risks and uncertainties are described more fully in Sangamo’s Securities and Exchange Commission, or SEC, filings and reports, including in Sangamo’s Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings and reports that Sangamo makes from time to time with the SEC. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law. Non-GAAP Financial Measures To supplement our financial results and guidance presented in accordance with GAAP, we present non-GAAP operating expenses, which excludes depreciation and amortization, stock-based compensation expense and impairment of goodwill, indefinite-lived intangible assets and long-lived assets from GAAP operating expenses. We believe that this non-GAAP financial measure, when considered together with our financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare our results from period to period and to our forward-looking guidance, and to identify operating trends in our business. We have excluded depreciation and amortization, and stock-based compensation expense because they are non-cash expenses that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented, and we have excluded impairment of goodwill, indefinite-lived intangible assets and long-lived assets to facilitate a more meaningful evaluation of our current operating performance and comparisons to our operating performance in other periods. This non-GAAP financial measure is in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. We encourage investors to carefully consider our results under GAAP, as well as our supplemental non-GAAP financial information, to more fully understand our business. SELECTED CONSOLIDATED FINANCIAL DATA (unaudited; in thousands, except per share data) Statement of Operations Data: Three Months Ended Year Ended December 31, December 31, 2023 2022 2023 2022 Revenues $ 2,042 $ 27,230 $ 176,232 $ 111,299 Operating expenses: Research and development 50,706 66,179 234,057 249,898 General and administrative 13,099 16,443 61,167 62,682 Impairment of goodwill and indefinite-lived intangible assets - - 89,485 - Impairment of long-lived assets 296 - 65,528 - Total operating expenses 64,101 82,622 450,237 312,580 Loss from operations (62,059 ) (55,392 ) (274,005 ) (201,281 ) Interest and other income, net 1,491 3,678 11,102 9,432 Loss before income taxes (60,568 ) (51,714 ) (262,903 ) (191,849 ) Income tax (benefit) expense (272 ) 259 (5,072 ) 429 Net loss $ (60,296 ) $ (51,973 ) $ (257,831 ) $ (192,278 ) Basic and diluted net loss per share $ (0.34 ) $ (0.32 ) $ (1.48 ) $ (1.25 ) Shares used in computing basic and diluted net loss per share 177,619 164,717 174,444 154,345 Selected Balance Sheet Data: December 31, 2023 December 31, 2022 Cash, cash equivalents, and marketable securities $ 81,002 $ 307,477 Total assets $ 165,320 $ 562,509 Total stockholders' equity $ 82,887 $ 294,958

- PHOENIX Study Did Not Meet Prespecified Primary or Secondary Endpoints - Data From 664-Participant Study Reinforce That AMX0035 is Generally Safe and Well-Tolerated - Within the Next Eight Weeks, Amylyx Will Continue to Engage With Regulatory Authorities and the ALS Community to Share Topline Data; Amylyx Will Share Plans for RELYVRIO/ALBRIOZA in ALS Which May Include Voluntarily Withdrawing RELYVRIO/ALBRIOZA From the Market - At This Time, RELYVRIO/ALBRIOZA Will Continue to be Available for People Living With ALS; Amylyx Has Voluntarily Decided to Pause Promotion; Related Patient Support Services Will Remain in Place - Studies With AMX0035 in Wolfram Syndrome (WS) and Progressive Supranuclear Palsy (PSP) to Continue Based on Data Supporting its Potential in These Diseases - Amylyx to Host Investor Conference Call Today, March 8, at 8:00 a.m. ET CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced topline results from PHOENIX, a global, 48-week, randomized, placebo-controlled Phase 3 clinical trial of AMX0035 (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]; RELYVRIO® in the U.S., ALBRIOZA™ in Canada) in people living with amyotrophic lateral sclerosis (ALS). PHOENIX did not meet its primary endpoint of reaching statistical significance (p=0.667) as measured by change from baseline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at Week 48, nor was there statistical significance seen in secondary endpoints. Amylyx plans to present the data from PHOENIX at an upcoming medical meeting and will publish the results in a medical journal later this year. Amylyx will continue to engage with regulatory authorities and the broader ALS community, including ALS specialists and other multidisciplinary experts, people living with ALS, and advocates, to discuss the results from PHOENIX within the next eight weeks and make informed decisions. Amylyx intends to share plans for RELYVRIO/ALBRIOZA in ALS, which may include voluntarily withdrawing RELYVRIO/ALBRIOZA from the market. At this time, RELYVRIO/ALBRIOZA and its related patient support program will continue to be available for people living with ALS. Amylyx has voluntarily decided to pause promotion of the medication during this time. “We are surprised and deeply disappointed by the PHOENIX results following the positive data from the CENTAUR trial. Our main priority at the moment is sharing the information with people living with ALS and their treating physicians; this is part of our continued commitment to them and our mission. Over the next eight weeks, our team will continue to engage with regulatory authorities and the ALS community to discuss the results from PHOENIX. We will be led in our decisions by two key principles: doing what is right for people living with ALS, informed by regulatory authorities and the ALS community, and by what the science tells us. On behalf of the entire Amylyx team, we are grateful to the ALS community and for the dedication of trial participants, investigators, and study site teams. With data collected from 664 participants in PHOENIX, we are certain there will be important learnings that will help inform future ALS research. We are steadfast in our commitment to the ALS community and our mission, including with AMX0035 where it has shown potential in neurodegenerative diseases such as Wolfram syndrome and progressive supranuclear palsy, and with AMX0114, our investigational antisense oligonucleotide targeting calpain-2, in ALS,” said Justin Klee and Joshua Cohen, Co-CEOs of Amylyx. PHOENIX Study Results: The Phase 3 PHOENIX study enrolled 664 adults living with ALS. Participants were randomized three-to-two to receive either AMX0035 or placebo, with both treatment groups receiving standard-of-care. Continuation of a stable dosing regimen of riluzole and/or edaravone was permitted. PHOENIX did not meet the primary endpoint: There was no significant difference observed between participants treated with AMX0035 and placebo in ALSFRS-R total score change from baseline at Week 48 (p=0.667). No significant difference was observed in the subset of participants who met the CENTAUR trial criteria. There were also no significant differences observed across secondary endpoints. Consistent safety and tolerability profile: AMX0035 was well-tolerated in PHOENIX. There were no new safety signals, reinforcing the favorable and manageable safety pro with AMX0035 to date. European participants who completed the 48-week randomized phase had the option to enroll in an open label extension of the trial of up to two years in duration, which remains ongoing. Science of AMX0035: AMX0035, a specially formulated oral fixed-dose combination of PB and TURSO, has been shown in numerous preclinical studies to have a robust, synergistic effect in targeting two different destructive neurodegenerative disease pathways by mitigating endoplasmic reticulum stress and the associated unfolded protein response and mitochondrial dysfunction thereby reducing neuronal cell death. Additionally, AMX0035 has been shown to also reduce markers associated with neurodegenerative diseases in clinical trials, including a reduction of tau, a key protein aggregate shared across several neurodegenerative diseases, and YKL-40, a marker of neuroinflammation. Update on Ongoing AMX0035 Studies: The global, randomized, double-blind, placebo-controlled Phase 3 ORION clinical study of AMX0035 in PSP remains ongoing. The first participant was dosed in December 2023, and the Company is planning for an interim analysis. Topline results continue to be anticipated in 2025 or 2026. Data from the ongoing 12-participant, single site, open-label Phase 2 HELIOS clinical study are demonstrating evidence of clinical activity of AMX0035 in Wolfram syndrome. This study is fully recruited, and the Company plans to present preliminary data in the second quarter of 2024. Investor Conference Call Information Amylyx’ management team will host a live conference call and webcast today, March 8, 2024, at 8:00 a.m. ET to discuss the results of the PHOENIX trial. To participate in the conference call, please dial +1 (877) 870-4263 (U.S.), +1 (855) 669-9657 (Canada), or +1 (412) 317-0790 (International) at least 10 minutes prior to the start time and ask to be joined into the Amylyx Pharmaceuticals call. All interested parties are invited to access a live broadcast of the call via a webcast, which will be available on the “Events and Presentations” page in the “Investors” section of the Company’s website at investors.amylyx.com/news-events/events. An archived webcast will be available on the Company's website approximately two hours after the conference call and will be available for replay for 90 days following the call. About the PHOENIX Trial PHOENIX was a 48-week, randomized, placebo-controlled, global Phase 3 clinical trial further evaluating the safety and efficacy of AMX0035 (sodium phenylbutyrate and taurursodiol) for the treatment of ALS. The primary efficacy outcome of the trial was change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score at 48 weeks. Secondary endpoints include quality of life patient-reported outcome assessments, overall survival, and respiratory function as measured by slow vital capacity (SVC). Safety and tolerability were also assessed. European participants who completed the 48-week trial had the option to enroll in an open-label extension (OLE) phase. During this phase, all participants receive AMX0035, and continued safety and efficacy measures will be assessed. About the CENTAUR Trial CENTAUR was a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Overall, reported rates of adverse events and discontinuations were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed data from CENTAUR is published in the New England Journal of Medicine (NEJM) and Muscle & Nerve. The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by The ALS Association, ALS Finding a Cure (a program of The Leandro P. Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General. About AMX0114 AMX0114 is an antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (Wallerian) degeneration pathway. Axonal degeneration has been recognized as an important early contributor to the clinical presentation and pathogenesis of ALS and other neurodegenerative diseases. Calpain-2 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves potent, dose-dependent, and durable knockdown of CAPN2 mRNA expression and calpain-2 protein levels in human motor neurons. Moreover, in preclinical efficacy studies, treatment with AMX0114 reduced extracellular neurofilament light chain levels following neurotoxic insult in iPSC-derived human motor neurons, and improved survival of iPSC-derived human motor neurons harboring ALS-linked, pathogenic TDP-43 mutations. About ALS Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than 90% of people with ALS have sporadic disease, showing no clear family history. ALS affects around 30,000 people in the U.S., and more than 30,000 people are estimated to be living with ALS in Europe (European Union and United Kingdom). People living with ALS have a median survival of approximately two years from diagnosis. About HELIOS The HELIOS trial (NCT05676034) is a 12-participant, open-label proof of biology, Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome (WS). About Wolfram Syndrome Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of WS include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. Genetic and experimental evidence suggest that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of WS. The prognosis of WS is poor, and many people with the disease die prematurely with severe neurological disabilities. About the ORION Trial The Phase 3 ORION trial (NCT06122662) is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo in people living with progressive supranuclear palsy (PSP). The ORION Phase 3 trial was designed and planned in collaboration with key global academic leaders, people living with PSP and their caregivers, and industry advocacy organizations. About PSP Progressive supranuclear palsy (PSP) is a sporadic, rare and adult-onset neurodegenerative disorder that affects walking and balance, eye movement, swallowing, and speech. People living with PSP have a life expectancy of six to eight years after initial diagnosis, and its epidemiology is similar to that of amyotrophic lateral sclerosis (ALS). PSP typically begins in late-middle age and rapidly progresses over time. The disease affects approximately seven in 100,000 people worldwide, and there are currently no disease-modifying therapies approved for the treatment of PSP. PSP is characterized by abnormal tau inclusions and is consequently also known as a tauopathy. Similar to other neurodegenerative diseases, pathophysiologic changes underlying PSP are multifactorial with several genetic and environmental factors likely contributing to tau dysfunction and aggregation. Multiple pathways, including genetic mutations, endoplasmic reticulum (ER) stress and the activation of unfolded protein response, mitochondrial dysfunction, and neuroinflammation have been implicated as contributors to tau dysfunction and aggregation. About AMX0035 / RELYVRIO® / ALBRIOZA™ AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the U.S.). It is approved as RELYVRIO® to treat amyotrophic lateral sclerosis (ALS) in adults in the U.S. and approved with conditions as ALBRIOZA™ for the treatment of ALS in Canada. AMX0035 is being studied for the potential treatment of other neurodegenerative diseases, and Amylyx is exploring its treatment in other populations and regions. The formulation of RELYVRIO, ALBRIOZA, and AMX0035 is identical. RELYVRIO® (sodium phenylbutyrate and taurursodiol) Safety Information for United States WARNINGS AND PRECAUTIONS Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction. Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO. Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist. Patients with disorders of enterohepatic circulation (e.g., biliary infection, active cholecystitis), severe pancreatic disorders (e.g., pancreatitis), and intestinal disorders that may alter concentrations of bile acids (e.g., ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions. Use in Patients Sensitive to High Sodium Intake RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (e.g., those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately. ADVERSE REACTIONS The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment. Please click here for RELYVRIO Full U.S. Prescribing Information. About Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative disease community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts and has operations in Canada, EMEA, and Japan. For more information, visit amylyx.com and follow us on LinkedIn and X, (formerly Twitter). For investors, please visit investors.amylyx.com. Forward-Looking Statements Statements contained in this press release and related comments in our earnings conference call regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, Amylyx’ expectations regarding: interactions with regulatory authorities; the continued availability of RELYVRIO/ALBRIOZA for people living with ALS while such interactions are ongoing; the pausing of promotion of RELYVRIO/ALBRIOZA; pathways for continued access for patients if RELYVRIO/ALBRIOZA are withdrawn from the market; the possibility for Amylyx to voluntarily withdraw RELYVRIO/ALBRIOZA from the market; the continued evaluation of AMX0035 in other neurodegenerative diseases, including the timing for expected data readouts in the ORION and HELIOS studies; and the evidence of biological activity of AMX0035 in Wolfram syndrome. Any forward-looking statements in this press release and related comments in the Company's conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.