CRISPR Therapeutics AG (CRSP)
SIC breadcrumb: Manufacturing > Chemicals And Allied Products > SIC 2836 Biological Products, (No Diagnostic Substances)
SEC company page: https://www.sec.gov/edgar/browse/?CIK=1674416. Latest filing source: 0001193125-26-048957.
Selected Fundamentals
| Metric | Value | Unit | FY | Filed |
|---|---|---|---|---|
| Revenue | 3,510,000 | USD | 2025 | 2026-02-12 |
| Net income | -581,599,000 | USD | 2025 | 2026-02-12 |
| Assets | 2,265,243,000 | USD | 2025 | 2026-02-12 |
Financials
Annual standardized facts from SEC companyfacts as of latest extracted filing date 2026-02-12. Source: https://data.sec.gov/api/xbrl/companyfacts/CIK0001674416.json. Derived margins, ratios, and free cash flow are computed from the extracted annual SEC facts.
| Metric | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 |
|---|---|---|---|---|---|---|---|---|---|---|
| Revenue | 3,124,000 | 289,590,000 | 719,000 | 914,963,000 | 1,198,000 | 371,206,000 | 37,314,000 | 3,510,000 | ||
| Net income | -23,177,000 | -68,357,000 | -164,981,000 | 66,858,000 | -348,865,000 | 377,661,000 | -650,175,000 | -153,610,000 | -366,252,000 | -581,599,000 |
| Operating income | -68,130,000 | -64,648,000 | -158,943,000 | 46,740,000 | -354,435,000 | 373,528,000 | -673,161,000 | -222,538,000 | -466,566,000 | -664,571,000 |
| Diluted EPS | -1.71 | -3.44 | 1.17 | -5.29 | 4.70 | -8.36 | -1.94 | -4.34 | -6.47 | |
| Operating cash flow | -52,860,000 | -70,093,000 | -96,239,000 | 56,677,000 | -238,366,000 | 538,972,000 | -495,741,000 | -260,375,000 | -142,774,000 | -345,014,000 |
| Capital expenditures | 3,016,000 | 7,814,000 | 2,773,000 | 6,684,000 | 18,358,000 | 81,705,000 | 37,188,000 | 9,470,000 | 1,901,000 | 914,000 |
| Assets | 344,962,000 | 271,346,000 | 489,016,000 | 1,066,752,000 | 1,827,966,000 | 2,751,877,000 | 2,243,057,000 | 2,229,571,000 | 2,242,034,000 | 2,265,243,000 |
| Liabilities | 112,116,000 | 83,514,000 | 96,821,000 | 127,327,000 | 163,732,000 | 352,417,000 | 367,578,000 | 346,768,000 | 309,954,000 | 343,430,000 |
| Stockholders' equity | 232,846,000 | 187,832,000 | 392,195,000 | 939,425,000 | 1,664,234,000 | 2,399,460,000 | 1,875,479,000 | 1,882,803,000 | 1,932,080,000 | 1,921,813,000 |
| Cash and cash equivalents | 315,520,000 | 239,758,000 | 456,649,000 | 943,771,000 | 1,168,620,000 | 923,031,000 | 211,885,000 | 389,477,000 | 298,257,000 | 347,559,000 |
| Free cash flow | -55,876,000 | -77,907,000 | -99,012,000 | 49,993,000 | -256,724,000 | 457,267,000 | -532,929,000 | -269,845,000 | -144,675,000 | -345,928,000 |
Ratios
| Metric | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 |
|---|---|---|---|---|---|---|---|---|---|---|
| Net margin | 23.09% | 41.28% | -41.38% | |||||||
| Operating margin | 16.14% | 40.82% | -59.95% | |||||||
| Return on equity | -9.95% | -36.39% | -42.07% | 7.12% | -20.96% | 15.74% | -34.67% | -8.16% | -18.96% | -30.26% |
| Return on assets | -6.72% | -25.19% | -33.74% | 6.27% | -19.08% | 13.72% | -28.99% | -6.89% | -16.34% | -25.67% |
| Liabilities / equity | 0.48 | 0.44 | 0.25 | 0.14 | 0.10 | 0.15 | 0.20 | 0.18 | 0.16 | 0.18 |
| Current ratio | 14.56 | 17.12 | 16.81 | 17.29 | 18.21 | 20.17 | 15.30 | 17.54 | 22.07 | 13.32 |
Financial Charts
Quarterly
Quarterly standardized facts from SEC companyfacts as of latest extracted filing date 2026-05-04. Source: https://data.sec.gov/api/xbrl/companyfacts/CIK0001674416.json.
| Quarter | End Date | Revenue | Net Income | Diluted EPS | Method |
|---|---|---|---|---|---|
| 2022-Q2 | 2022-06-30 | -2.40 | reported discrete quarter | ||
| 2022-Q3 | 2022-09-30 | -2.24 | reported discrete quarter | ||
| 2023-Q1 | 2023-03-31 | -0.67 | reported discrete quarter | ||
| 2023-Q2 | 2023-03-31 | -53,065,000 | reported discrete quarter | ||
| 2023-Q2 | 2023-06-30 | 70,000,000 | -0.98 | reported discrete quarter | |
| 2023-Q3 | 2023-06-30 | -77,740,000 | reported discrete quarter | ||
| 2023-Q3 | 2023-09-30 | 0.00 | -1.41 | reported discrete quarter | |
| 2023-Q4 | 2023-12-31 | 201,206,000 | 89,347,000 | derived Q4 = FY annual - nine-month YTD | |
| 2024-Q1 | 2024-03-31 | 504,000 | -116,591,000 | -1.43 | reported discrete quarter |
| 2024-Q2 | 2024-03-31 | -116,591,000 | reported discrete quarter | ||
| 2024-Q2 | 2024-06-30 | 517,000 | -1.49 | reported discrete quarter | |
| 2024-Q3 | 2024-06-30 | -126,408,000 | reported discrete quarter | ||
| 2024-Q3 | 2024-09-30 | 602,000 | -1.01 | reported discrete quarter | |
| 2024-Q4 | 2024-12-31 | 35,691,000 | -37,311,000 | derived Q4 = FY annual - nine-month YTD | |
| 2025-Q1 | 2025-03-31 | 865,000 | -135,996,000 | -1.58 | reported discrete quarter |
| 2025-Q2 | 2025-03-31 | -135,996,000 | reported discrete quarter | ||
| 2025-Q2 | 2025-06-30 | 892,000 | -2.40 | reported discrete quarter | |
| 2025-Q3 | 2025-06-30 | -208,549,000 | reported discrete quarter | ||
| 2025-Q3 | 2025-09-30 | 889,000 | -1.17 | reported discrete quarter | |
| 2025-Q4 | 2025-12-31 | 864,000 | -130,613,000 | derived Q4 = FY annual - nine-month YTD | |
| 2026-Q1 | 2026-03-31 | 1,458,000 | -122,931,000 | -1.28 | reported discrete quarter |
Quarterly Charts
Macro Cross-References
- CPIAUCSL - Consumer Price Index for All Urban Consumers: All Items in U.S. City Average
- UNRATE - Unemployment Rate
- FEDFUNDS - Federal Funds Effective Rate
- CES0500000003 - Average Hourly Earnings of All Employees, Total Private
- DFEDTARU - Federal Funds Target Range - Upper Limit
- DFEDTARL - Federal Funds Target Range - Lower Limit
- DGS3MO - Market Yield on U.S. Treasury Securities at 3-Month Constant Maturity
- DGS2 - Market Yield on U.S. Treasury Securities at 2-Year Constant Maturity
- DGS10 - Market Yield on U.S. Treasury Securities at 10-Year Constant Maturity
- DGS30 - Market Yield on U.S. Treasury Securities at 30-Year Constant Maturity
- T10Y2Y - 10-Year Treasury Constant Maturity Minus 2-Year Treasury Constant Maturity
- CPILFESL - Consumer Price Index for All Urban Consumers: All Items Less Food and Energy
- CPIUFDSL - Consumer Price Index for All Urban Consumers: Food
- CPIENGSL - Consumer Price Index for All Urban Consumers: Energy
- CUSR0000SAH1 - Consumer Price Index for All Urban Consumers: Shelter
- PCEPI - Personal Consumption Expenditures: Chain-type Price Index
- PCEPILFE - Personal Consumption Expenditures Excluding Food and Energy: Chain-type Price Index
- PPIACO - Producer Price Index by Commodity: All Commodities
- T10YIE - 10-Year Breakeven Inflation Rate
- U6RATE - Total Unemployed, Plus All Marginally Attached Workers Plus Total Employed Part Time for Economic Reasons
- PAYEMS - All Employees, Total Nonfarm
- CIVPART - Labor Force Participation Rate
- EMRATIO - Employment-Population Ratio
- UNEMPLOY - Unemployed
- CE16OV - Employment Level
- ICSA - Initial Claims
- JTSJOL - Job Openings: Total Nonfarm
- JTSQUR - Quits: Total Nonfarm
- GDPC1 - Real Gross Domestic Product
- A191RL1Q225SBEA - Real Gross Domestic Product: Percent Change from Preceding Period
- INDPRO - Industrial Production: Total Index
- TCU - Capacity Utilization: Total Index
- HOUST - New Privately-Owned Housing Units Started: Total Units
- PERMIT - New Privately-Owned Housing Units Authorized in Permit-Issuing Places: Total Units
- RSAFS - Advance Retail Sales: Retail Trade
- PCE - Personal Consumption Expenditures
- DSPIC96 - Real Disposable Personal Income
- PSAVERT - Personal Saving Rate
- M2SL - M2
- BOPGSTB - U.S. International Trade in Goods and Services: Balance
- MSPUS - Median Sales Price of Houses Sold for the United States
- HSN1F - New One Family Houses Sold: United States
- RHORUSQ156N - Homeownership Rate in the United States
- TTLCONS - Total Construction Spending: Total Construction in the United States
- RRVRUSQ156N - Rental Vacancy Rate in the United States
- TOTALSL - Total Consumer Credit Owned and Securitized
- REVOLSL - Revolving Consumer Credit Owned and Securitized
- DRCCLACBS - Delinquency Rate on Credit Card Loans, All Commercial Banks
- GDP - Gross Domestic Product
- GPDI - Gross Private Domestic Investment
- GCE - Government Consumption Expenditures and Gross Investment
- PCEC - Personal Consumption Expenditures
- NETEXP - Net Exports of Goods and Services
- GFDEBTN - Federal Debt: Total Public Debt
- GFDEGDQ188S - Federal Debt: Total Public Debt as Percent of Gross Domestic Product
- FYFSD - Federal Surplus or Deficit
- FGRECPT - Federal Government Current Receipts
- FGEXPND - Federal Government: Current Expenditures
- MANEMP - All Employees, Manufacturing
- USCONS - All Employees, Construction
- USTRADE - All Employees, Retail Trade
- USFIRE - All Employees, Financial Activities
- USGOVT - All Employees, Government
- AWHAETP - Average Weekly Hours of All Employees, Total Private
- DGORDER - Manufacturers' New Orders: Durable Goods
- NEWORDER - Manufacturers' New Orders: Nondefense Capital Goods Excluding Aircraft
- BUSINV - Total Business Inventories
- EXPGS - Exports of Goods and Services
- IMPGS - Imports of Goods and Services
- IR - Import Price Index (End Use): All Commodities
- PPIFIS - Producer Price Index by Commodity: Final Demand
Latest quarter (10-Q)
Latest 10-Q source: 0001193125-26-204188.
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations The following discussion and analysis of our financial condition and results of operations should be read in conjunction with (i) our unaudited condensed consolidated financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q and (ii) our audited consolidated financial statements and related notes and management’s discussion and analysis of financial condition and results of operations included in our Annual Report on Form 10-K for the year ended December 31, 2025 filed with the Securities and Exchange Commission, or the SEC, on February 12, 2026. Some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q, including information with respect to our plans and strategy for our business and impact and potential impacts on our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including, without limitation, those factors set forth in the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2025 and the “Risk Factors” section of subsequent Quarterly Reports on Form 10-Q, our actual results or timing of certain events could differ materially from the results or timing described in, or implied by, these forward-looking statements. Overview Our mission is to create transformative gene-based medicines for serious human diseases. We are a leading biopharmaceutical company focused on the development of CRISPR-based therapeutics, including by using CRISPR/Cas9 technology. We have established a portfolio of therapeutic programs spanning four core franchises: hemoglobinopathies, in vivo approaches, CAR-T and regenerative medicine. Depending on the program, we take either an ex vivo approach, in which we edit cells outside of the human body before administering them to the patient, or an in vivo editing approach, where we deliver the CRISPR-based therapeutic directly to target cells within the human body. CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA. We have advanced this technology from discovery to an approved medicine with unparalleled speed, culminating in the landmark first approval of a CRISPR-based therapy, CASGEVY (exagamglogene autotemcel [exa-cel]), in 2023 with our collaborators at Vertex Pharmaceuticals Incorporated, or Vertex. We continue to innovate on our platform to develop next-generation technologies that can enable new therapies. We are developing other technologies, including delivery technologies and other gene editing technologies, like SyNTase. Through our efforts, we aim to unlock the full potential of gene-based therapeutics to create medicines that can transform people’s lives. We believe that our innovative research, translational expertise and clinical development experience position us as a leader in the development of CRISPR-based therapeutics and may enable us to create an entirely new class of highly effective and potentially curative therapies for patients with both common and rare diseases for whom current biopharmaceutical approaches have had limited success. Hemoglobinopathies CASGEVY CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin in red blood cells, which can compensate for the defective adult hemoglobin in patients with sickle cell disease, or SCD, or transfusion-dependent beta thalassemia, or TDT. CASGEVY is the first therapy to emerge from our strategic partnership with Vertex and is being advanced under a joint development and commercialization agreement between us and Vertex and certain of its affiliates. In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world. To date, CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland and certain countries in the Middle East for the treatment of eligible patients 12 years and older with SCD or TDT. We and Vertex continue to investigate CASGEVY, including in clinical trials designed to assess the safety and efficacy of a single dose of CASGEVY in patients 12 to 35 years of age with severe SCD and TDT, respectively, two pivotal trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion. Overall, CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of this therapy as a potential one-time functional cure for people with severe SCD and TDT. Additional candidates We continue to advance our internally developed targeted conditioning program, as well as in vivo hematopoietic stem cell editing approaches utilizing lipid nanoparticle-mediated delivery through preclinical studies. Both initiatives could significantly expand the addressable patient populations for SCD and TDT. In Vivo Liver Editing We have established a leading platform for in vivo gene editing and are rapidly advancing a pipeline of in vivo gene editing candidates that target the liver, taking advantage of validated lipid nanoparticle, or LNP, delivery technologies, and aim to treat 19 Table of Contents diseases where we can produce a strong therapeutic effect by safely disrupting a gene with well-understood genetic association. We have established a proprietary LNP delivery platform to enable gene-editing in the liver using both CRISPR/Cas9 and our novel, proprietary SyNTase editing technologies. Our in vivo portfolio includes cardiovascular programs, such as CTX310, directed towards angiopoietin-related protein 3, which is currently in an ongoing Phase 1b clinical trial in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia. Additional candidates In addition, we have a number of earlier stage investigational in vivo programs leveraging gene disruption in the liver for both common and rare diseases, including CTX340, directed towards angiotensinogen for the treatment of refractory hypertension; our next-generation LPA program, CTX321 directed towards LPA, the gene encoding apolipoprotein(a), a major component of lipoprotein(a), or Lp(a), in development for patients with elevated Lp(a), and CTX460, directed towards SERPINA1 using our proprietary SyNTase editing platform, for the treatment of alpha-1 antitrypsin deficiency. CTX340, CTX321 and CTX460 are currently in IND/CTA-enabling studies. We are also pursuing additional delivery technologies, including LNPs, for delivery to tissues beyond the liver, including hematopoietic stem cells and T cells. siRNA-based Programs Our siRNA-based portfolio includes clinical-stage programs in cardiovascular and thromboembolic diseases, developed in collaboration with Sirius Therapeutics and certain of its affiliates, or Sirius. CTX611 is a novel double-stranded, long-acting siRNA, designed to target the human coagulation factor XI, or FXI, messenger RNA and inhibit FXI protein expression. Through modulation of the intrinsic coagulation pathway, CTX611 is intended to provide anticoagulant and antithrombotic effects. Supported by clinical experience conducted by Sirius in two Phase 1 clinical trials, CTX611 is being developed as a long-acting FXI inhibitor with the potential to support infrequent, including semi-annual, subcutaneous administration. CTX611 is in ongoing Phase 2 clinical trials, including in patients undergoing total knee arthroplasty. CAR-T We believe CRISPR/Cas9 has the potential to create the next generation of CAR-T cell therapies that may have a superior product profile and allow broader patient access compared to current autologous therapies. We are advancing several cell therapy programs in both autoimmune and immuno-oncology indications. Zugocabtagene geleucel Our lead next-generation product candidate, zugocabtagene geleucel (zugo-cel; formerly CTX112), incorporates edits designed to enhance CAR-T potency, reduce CAR-T exhaustion and evade the immune system. As a result of the next-generation edits, zugo-cel exhibits increased manufacturing robustness, with a higher and more consistent number of CAR-T cells produced per batch. We are producing zugo-cel for clinical trials at our internal GMP manufacturing facility in Framingham, Massachusetts. Zugo-cel continues to advance in both autoimmune disease and hematologic malignancies. In autoimmune disease, it is being investigated in ongoing clinical trials designed to assess the safety and efficacy of the product candidate in adult patients across multiple indications, including an initial clinical trial in systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis; a second clinical trial in immune thrombocytopenia purpura and warm autoimmune hemolytic anemia; and a third clinical trial in autoimmune neurologic diseases, including progressive multiple sclerosis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated Disease (MOGAD), N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated Protein 1 (LGI1) autoimmune encephalitis, and stiff person syndrome. In immuno-oncology, the Phase 1/2 clinical trial in adult patients with relapsed or refractory B-cell malignancies who have received at least two prior lines of therapy is ongoing. Eligible disease subtypes include large B-cell lymphoma, or LBCL, follicular lymphoma grade 1-3a, marginal zone lymphoma, and mantle cell lymphoma. Initial positive clinical data generated through December 2025 support the advancement of zugo-cel into the Phase 2 portion of the ongoing Phase 1/2 trial. We have also established a collaboration and clinical supply agreement with Eli Lilly to evaluate zugo-cel together with pirtobrutinib in aggressive B-cell lymphomas, further expanding the program’s development in oncology. Zugo-cel has been granted regenerative medicine advanced therapy designation by the U.S. Food and Drug Administration for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma. Additional candidates Our CRISPR/Cas9 platform enables us to innovate continuously by incorporating incremental edits into next-generation products. We are advancing several additional investigational CAR-T programs. In addition, we are developing both transient and integrated in vivo CAR-T therapies by targeting T cells with LNPs and leveraging our delivery, mRNA, and gene editing expertise. Regenerative Medicine 20 Table of Contents We continue to advance our regenerative medicine portfolio, including in diabetes. We are advancing CTX213, a deviceless beta cell replacement product candidate consisting of unencapsulated precursor islet cells derived from induced pluripotent stem cells for the treatment of type 1 diabetes, or T1D. To date, CTX213 has demonstrated preclinical efficacy data via direct administration. In addition, we have granted a non-exclusive license to certain of our CRISPR/Cas9 intellectual property to Vertex to accelerate Vertex’s development of hypoimmune cell therapies for T1D in exchange for certain milestones and royalties. Next-generation Editing Modalities While we have made significant progress with our current portfolio of programs, we recognize that we may be able to bring transformative therapies to even more patients by continuing to innovate to unlock the full potentia [Excerpt truncated for page length; source filing is linked above.]
Latest 10-K MD&A
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations. You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K. Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-K, including information with respect to our plans and strategy for our business and related financing, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Annual Report on Form 10-K, our actual results could differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis. Overview Our mission is to create transformative gene-based medicines for serious human diseases. We are a leading biopharmaceutical company focused on the development of CRISPR-based therapeutics, including by using CRISPR/Cas9 technology. We have established a portfolio of therapeutic programs spanning four core franchises: hemoglobinopathies, in vivo approaches, CAR T, and regenerative medicine. Depending on the program, we take either an ex vivo approach, in which we edit cells outside of the human body before administering them to the patient, or an in vivo editing approach, where we deliver the CRISPR-based therapeutic directly to target cells within the human body. CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA. We have advanced this technology from discovery to an approved medicine with unparalleled speed, culminating in the landmark first approval of a CRISPR-based therapy, CASGEVY (exagamglogene autotemcel [exa-cel]), in 2023 with our collaborators at Vertex Pharmaceuticals Incorporated, or Vertex. We continue to innovate on our platform to develop next-generation technologies that can enable new therapies. We are developing other technologies, including delivery technologies and other gene editing technologies, like SyNTase. Through our efforts, we aim to unlock the full potential of gene-based therapeutics to create medicines that can transform people’s lives. We believe that our innovative research, translational expertise, and clinical development experience, position us as a leader in the development of CRISPR-based therapeutics and may enable us to create an entirely new class of highly effective and potentially curative therapies for patients with both common and rare diseases for whom current biopharmaceutical approaches have had limited success. Hemoglobinopathies CASGEVY CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin in red blood cells, which can compensate for the defective adult hemoglobin in patients with SCD and TDT. CASGEVY is the first therapy to emerge from our strategic partnership with Vertex and is being advanced under a joint development and commercialization agreement between us and Vertex and certain of its affiliates. 99 In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world. To date, CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland and certain countries in the Middle East for the treatment of eligible patients 12 years and older with SCD or TDT. We and Vertex continue to investigate CASGEVY, including in clinical trials designed to assess the safety and efficacy of a single dose of CASGEVY in patients 12 to 35 years of age with severe SCD and TDT, respectively, two pivotal trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion. Overall, CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of this therapy as a potential one-time functional cure for people with severe SCD and TDT. Additional Candidates We continue to advance our internally developed targeted conditioning program, as well as in vivo hematopoietic stem cell editing approaches utilizing lipid nanoparticle-mediated delivery through preclinical studies. Both initiatives could significantly expand the addressable patient populations for SCD and TDT. In Vivo Liver Editing We have established a leading platform for in vivo gene editing and are rapidly advancing a pipeline of in vivo gene editing candidates that target the liver, taking advantage of validated lipid nanoparticle, or LNP, delivery technologies, and aim to treat diseases where we can produce a strong therapeutic effect by safely disrupting a gene with well-understood genetic association. We have established a proprietary LNP delivery platform to enable gene-editing in the liver using both CRISPR/Cas9 and our novel, proprietary SyNTase editing technologies. Our in vivo portfolio includes cardiovascular programs, such as CTX310, directed towards angiopoietin-related protein 3 or ANGPTL3, which is currently in an ongoing Phase 1b clinical trial in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia. Additional candidates In addition, we have a number of earlier stage investigational in vivo programs leveraging gene disruption in the liver for both common and rare diseases, including CTX340, directed towards angiotensinogen for the treatment of refractory hypertension; our next-generation LPA program, CTX321 directed towards LPA, the gene encoding apolipoprotein(a), a major component of lipoprotein(a), or Lp(a), and CTX460, directed towards SERPINA1 using our proprietary SyNTase editing platform, for the treatment of alpha-1 antitrypsin deficiency. CTX340 and CTX321 are currently in IND-enabling studies in patients with refractory hypertension and in patients with elevated Lp(a), which has been shown to have an independent association with major adverse cardiovascular events, respectively. We are progressing CTX460 through preclinical studies. We are also pursuing additional delivery technologies, including LNPs, for delivery to tissues beyond the liver, including hematopoietic stem cells and T cells. siRNA-based Programs Our siRNA-based portfolio includes clinical-stage programs in cardiovascular and thromboembolic diseases, developed in collaboration with Sirius Therapeutics and certain of its affiliates, or Sirius. CTX611 (formerly known as SRSD107) is a novel double-stranded, long-acting siRNA, designed to target the human coagulation factor XI, or FXI, messenger RNA and inhibit FXI protein expression. Through modulation of the intrinsic coagulation pathway, CTX611 is intended to provide anticoagulant and antithrombotic effects. Supported by clinical experience conducted by Sirius in two Phase 1 clinical trials, CTX611 is being developed as a long-acting FXI inhibitor with the potential to support infrequent, including semi-annual, subcutaneous administration. CTX611 is in an ongoing Phase 2 clinical trial in patients undergoing total knee arthroplasty. CAR T We believe CRISPR/Cas9 has the potential to create the next generation of CAR T cell therapies that may have a superior product profile and allow broader patient access compared to current autologous therapies. We are advancing cell therapy programs for autoimmune indications and oncology. Zugocabtagene geleucel Our lead next-generation product candidate, zugocabtagene geleucel (zugo-cel; formerly CTX112), incorporates edits designed to enhance CAR T potency, reduce CAR T exhaustion and evade the immune system. As a result of the next-generation edits, zugo-cel exhibits increased manufacturing robustness, with a higher and more consistent number of CAR T cells produced per batch. We are producing zugo-cel for clinical trials at our internal GMP manufacturing facility in Framingham, Massachusetts. Zugo-cel continues to advance in both autoimmune disease and hematologic malignancies. 100 In autoimmune disease, it is being investigated in an ongoing clinical trial designed to assess the safety and efficacy of the product candidate in adult patients with systemic lupus erythematosus, or SLE, systemic sclerosis, and inflammatory myositis, and a second clinical trial in immune thrombocytopenia purpura and warm autoimmune hemolytic anemia. In oncology, the Phase 1/2 clinical trial in adult patients with relapsed or refractory B-cell malignancies who have received at least two prior lines of therapy is ongoing. Eligible disease subtypes include large B-cell lymphoma, or LBCL, follicular lymphoma grade 1-3a, marginal zone lymphoma, and mantle cell lymphoma. Initial positive clinical data generated through December 2025 support the advancement of zugo-cel into the Phase 2 portion of the ongoing Phase 1/2 trial. We have also established a collaboration and clinical supply agreement with Eli Lilly to evaluate zugo-cel together with pirtobrutinib in aggressive B-cell lymphomas, further expanding the program’s development in oncology. Zugo-cel has been granted RMAT designation by the U.S. Food and Drug Administration for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma. Additional candidates Our CRISPR/Cas9 platform enables us to innovate continuously by incorporating incremental edits into next-generation products. We are advancing several additional investigational CAR T programs. In addition, we are developing both transient and integrated in vivo CAR T therapies by targeting T cells with LNPs and leveraging our delivery, mRNA, and gene editing expertise. Regenerative Medicine We continue to advance our regenerative medicine portfolio, including in diabetes. We are advancing CTX213, a deviceless beta cell replacement product candidate consisting of unencapsulated precursor islet cells derived from induced pluripotent stem cells for the treatment of T1D. To date, CTX213 has demonstrated preclinical efficacy data via direct administration. In addition, we have granted a non-exclusive license to certain of our CRISPR/Cas9 intellectual property to Vertex to accelerate Vertex’s development of hypoimmune cell therapies for T1D in exchange for certain milestones and royalties. Next-generation Editing Modalities While we have made significant progress with our current portfolio of programs, we recognize that we may be able to bring transformative therapies to even more patients by continuing to innovate to unlock the full potential of gene editing. We are focused on innovating next-generation editing modalities. For example, we have developed a proprietary, next-generation, site-specific gene correction platform called SyNTase editing. In addition, we are also developing technologies to enable whole gene correction and insertion via non-viral DNA delivery and all-RNA systems. Partnerships Given the numerous potential therapeutic applications for CRISPR/Cas9, we have partnered strategically to broaden the indications we can pursue and accelerate development of programs by accessing specific technologies and/or disease-area expertise. We maintain broad partnerships to develop gene editing-based therapeutics in specific disease areas. For additional information regarding certain of these partnerships, please see “Business—Strategic Partnerships and Collaborations.” Hemoglobinopathies. In 2015, we partnered with Vertex and entered into a strategic collaboration, option and license agreement, which focused on the discovery and development of gene-based treatments for hemoglobinopathies and cystic fibrosis using CRISPR/Cas9 gene-editing technology. In 2017, Vertex exercised its option to co-develop and co-commercialize the hemoglobinopathies program and we entered into a joint development and commercialization agreement with Vertex, which we amended and restated in 2021, pursuant to which, among other things, we are co-developing and co-commercializing CASGEVY for TDT and SCD. siRNA. In May 2025, we partnered with Sirius and entered into the Sirius Agreement pursuant to which, among other things, we and Sirius will collaborate on the research, development, manufacture, commercialization and use of the Sirius Collaboration Products, including co-development and co-commercialization of CTX611; and (2) Sirius granted us options to exclusively license Sirius siRNA technology to target up to two licensed targets from a list of seven reserved targets for the research, develop, manufacture and commercialization of siRNA Licensed Products, For the first Sirius Collaboration Product successfully developed, we will be the lead party responsible for commercialization efforts in the United States and Sirius will be the lead party responsible for commercialization efforts in Greater China. Other Partnerships. We have entered into a number of additional collaborations, research and license agreements in other therapeutic areas, including additional agreements with Vertex including for the treatment of Duchenne muscular dystrophy and myotonic dystrophy type 1, as well as diabetes, and others, including to support and complement our hematopoietic stem cell, CAR T, in vivo and diabetes programs and platform. Financial Overview 101 Since our inception in October 2013, we have devoted substantially all of our resources to our research and development efforts, identifying potential product candidates, undertaking drug discovery and preclinical development activities, building and protecting our intellectual property estate, establishing internal manufacturing capabilities, organizing and staffing our company, business planning, raising capital and providing general and administrative support for these operations. To date, we have primarily financed our operations through private placements of our preferred shares, common share issuances, convertible loans and payments related to certain of our license and collaboration agreements with strategic partners. We have a history of recurring losses and expect to continue to incur losses for the foreseeable future; however, we have been in a net income position in certain previous years due to certain payments associated with our collaboration and license agreements with Vertex. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase as we continue our current research programs and development activities; seek to identify additional research programs and additional product candidates; conduct initial drug application supporting preclinical studies and initiate clinical trials for our product candidates; pursue business development activities; initiate preclinical testing and clinical trials for any other product candidates we identify and develop; seek regulatory approval for our product candidates; maintain, defend, protect and expand our intellectual property estate; further develop our gene editing platform; hire additional research, clinical and scientific personnel; incur facilities costs associated with such personnel growth; continue to develop internal manufacturing capabilities and infrastructure; and incur additional costs associated with operating as a public company. Revenue Recognition We have not generated any revenue to date from sales of any wholly-owned product. No collaboration revenue was recognized for the year ended December 31, 2025. During the years ended December 31, 2024 and 2023, we recognized $35.0 million and $370.0 million, respectively, of collaboration revenue, which is primarily related to our collaboration and license agreements with Vertex. For the years ended December 31, 2025, 2024 and 2023, we generated $3.5 million, $2.3 million and $1.2 million, respectively, of grant revenue related to certain contracts with not-for-profit entities. For additional information about our revenue recognition policy, see Note 2 and Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K. Research and Development Expenses Research and development expenses consist primarily of costs incurred for our research activities, including our product discovery efforts and the development of our product candidates, which include: • employee-related expenses, including salaries, benefits and equity-based compensation expense; • costs of services performed by third parties that conduct research and development and preclinical and clinical activities on our behalf; • costs of purchasing lab supplies and non-capital equipment used in our preclinical activities and in manufacturing preclinical study materials, as well as supplies and materials used to manufacture clinical drug material; • consultant fees; • facility costs, including rent, depreciation and maintenance expenses; and • fees and other payments related to acquiring and maintaining licenses under certain of our third-party licensing agreements. Our external research and development expenses support our various preclinical and clinical programs, and as such we do not break down external research and development expenses further. Our internal research and development expenses consist of payroll and benefits expenses, facilities expense, and other indirect research and development expenses incurred in support of overall research and development activities and as such are not allocated to a specific development stage or therapeutic area. Research and development costs are expensed as incurred. Nonrefundable advance payments for research and development goods or services to be received in the future are deferred and capitalized. The capitalized amounts are expensed as the related goods are delivered or the services are performed. At this time, we cannot reasonably estimate or know the nature, timing or estimated costs of the efforts that will be necessary to complete the development of any product candidates we may identify and develop. This is due to the numerous risks and uncertainties associated with developing such product candidates, including the uncertainty of: • successful completion of preclinical studies and IND-enabling studies; • successful enrollment in, and completion of, clinical trials; • receipt of marketing approvals from applicable regulatory authorities; • establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers; • obtaining and maintaining patent and trade secret protection and non-patent exclusivity; • launching commercial sales of the product, if and when approved, whether alone or in collaboration with others; 102 • acceptance of the product, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies and treatment options; • a continued acceptable safety profile following approval; • enforcing and defending intellectual property and proprietary rights and claims; and • achieving desirable medicinal properties for the intended indications. A change in the outcome of any of these variables with respect to the development of any product candidates or the subsequent commercialization of any product candidates we may successfully develop could significantly change the costs, timing and viability associated with the development of that product candidate. Research and development activities are central to our business model. We expect to continue to incur research and development costs consistent with research and development at companies of our size and stage of development, which may increase in the foreseeable future as our current development programs progress, new programs are added and we continue to prepare regulatory filings. These increases will likely include the costs related to the implementation and expansion of clinical trial sites and related patient enrollment, monitoring, program management and manufacturing expenses for current and future clinical trials. Acquired In-Process Research and Development Expenses Asset acquisition costs related to acquired technology are expensed as acquired in-process research and development at the point that they have no established alternative future use. We classify asset acquisitions of acquired in-process research and development as investing activities on our consolidated statements of cash flows. General and Administrative Expenses General and administrative expenses consist primarily of employee related expenses, including salaries, benefits and equity-based compensation, for personnel in executive, finance, accounting, business development, human resources and other general and administrative functions. Other significant costs include facility costs not otherwise included in research and development expenses, legal fees relating to patent and corporate matters and fees for accounting and consulting services. We expect to continue to incur general and administrative expenses consistent with general and administrative functions at research and development companies of our size and stage of development, which may increase in the future to support continued research and development activities, and potential commercialization of our product candidates. In addition, we anticipate ongoing expenses related to the reimbursements of third-party patent related expenses in connection with certain of our in-licensed intellectual property. Collaboration Expense, Net Collaboration expense, net, consists of operating expenses under our collaboration with Vertex for the hemoglobinopathies program. Other Income (Expense), Net Other income, net consists primarily of interest income earned on investments, as well as the change in fair value of corporate equity securities. Critical Accounting Policies and Significant Judgments and Estimates This discussion and analysis of our financial condition and results of operations is based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles. We believe that several accounting policies are important to understanding our historical and future performance. We refer to these policies as critical because these specific areas generally require us to make judgments and estimates about matters that are uncertain at the time we make the estimate, and different estimates—which also would have been reasonable—could have been used. On an ongoing basis, we evaluate our estimates and judgments, including those described in greater detail below. We base our estimates on historical experience and other market-specific or other relevant assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. While our significant accounting policies are described in more detail in the notes to our financial statements included elsewhere in this Annual Report on Form 10-K, we believe that the following accounting policies are the most critical to aid you in fully understanding and evaluating our financial condition and results of operations. 103 Revenue Accounting Standards Codification Topic 606, Revenue from Contracts with Customers, or ASC 606, applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases and collaboration arrangements. To determine revenue recognition for arrangements that an entity determines are within the scope of ASC 606, the entity performs the following five steps: 1) Identify the contract with the customer A contract with a customer exists when (i) we enter into an enforceable contract with a customer that defines each party’s rights regarding the goods or services to be transferred and identifies the related payment terms, (ii) the contract has commercial substance and (iii) we determine that collection of substantially all consideration for goods and services that are transferred is probable based on the customer’s intent and ability to pay the promised consideration. 2) Identify the performance obligations in the contract Performance obligations promised in a contract are identified based on the goods and services that will be transferred to the customer that are both capable of being distinct, whereby the customer can benefit from the good or service either on its own or together with other available resources, and are distinct in the context of the contract, whereby the transfer of the good or service is separately identifiable from other promises in the contract. To the extent a contract includes multiple promised goods and services, we must apply judgment to determine whether promised goods and services are capable of being distinct and distinct in the context of the contract. If these criteria are not met, the promised goods and services are accounted for as a combined performance obligation. 3) Determine the transaction price The transaction price is determined based on the consideration to which we will be entitled in exchange for transferring goods and services to the customer. To the extent the transaction price includes variable consideration, such as research, development, regulatory and commercial milestones, we determine if it is probable that we will receive such amounts and there is no risk of a significant revenue reversal. When we cannot conclude that receipt of such amounts is probable, we constrain the related variable consideration resulting in its exclusion from transaction consideration. In determining the portion of the transaction consideration to be constrained, we consider the probability and uncertainty that the related research, developmental, regulatory and commercial milestones will be achieved given the nature of research and clinical development and the stage of the underlying programs. This assessment is performed at each reporting period. In making this evaluation, we consider both internal and external information available, including information from industry publications and other relevant factors. Changes to the constraint of variable consideration can have a material effect on the amount of revenue recognized in the period. 4) Allocate the transaction consideration to performance obligations in the contract If the contract contains a single performance obligation, the entire transaction consideration is allocated to the single performance obligation. Contracts that contain multiple performance obligations require an allocation of the transaction consideration to each performance obligation on a relative standalone selling price basis unless the transaction consideration is variable and meets the criteria to be allocated entirely to a performance obligation or to a distinct service that forms part of a single performance obligation. The consideration to be received is allocated among the separate performance obligations based on relative standalone selling prices. In determining these estimated standalone selling prices, we make a number of significant judgments including, for licenses, management’s assumptions regarding probability weighted projected discounted cash flows for each of the collaboration development programs. The estimated standalone selling prices are sensitive to changes in assumptions, such as probabilities of scientific success, discount rate and certain assumptions that form the basis of forecasted cash flows. In developing these assumptions, management considers both internal and external information available, including information from other guideline companies within the same industry and other relevant factors. Changes to these assumptions can have a material effect on the allocation of the transaction consideration to performance obligations, as well as the amount and timing of revenue recognized. 5) Recognize revenue when or as we satisfy a performance obligation We satisfy performance obligations over time or at a point in time, depending on the nature of the performance obligation. Revenue is recognized over time if the customer simultaneously receives and consumes the benefits provided by the entity’s performance, the entity’s performance creates or enhances an asset that the customer controls as the asset is created or enhanced, or the entity’s performance does not create an asset with an alternative use to the entity and the entity has an enforceable right to payment for performance completed to date. If the entity does not satisfy a performance obligation over time, the related performance obligation is satisfied at a point in time by transferring the control of a promised good or service to a customer. Collaboration Arrangements We record the elements of our collaboration agreements that represent joint operating activities in accordance with Accounting Standards Codification Topic 808, Collaborative Arrangements, or ASC 808. Accordingly, the elements of the collaboration agreements that represent activities in which both parties are active participants and to which both parties are exposed to the 104 significant risks and rewards that are dependent on the commercial success of the activities, are recorded as collaborative arrangements. We evaluate the proper presentation of the commercial activities and the profit and loss sharing associated with the collaboration agreements. ASC 808 states that when payments between parties in a collaborative arrangement are not within the scope of other authoritative accounting literature, the income statement classification should be based on the nature of the arrangement, the nature of its business operations and the contractual terms of the arrangement. To the extent that these payments are not within the scope of other authoritative accounting literature, the income statement classification for the payments shall be based on an analogy to authoritative accounting literature or if there is no appropriate analogy, a reasonable, rational, and consistently applied accounting policy election. Accrued research and development expenses As part of the process of preparing our financial statements, we are required to estimate our accrued expenses. This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual cost. The majority of our service providers invoice us monthly in arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in our financial statements based on facts and circumstances known to us at that time. Examples of estimated accrued research and development expenses include fees paid to: • CROs in connection with clinical studies; • investigative sites in connection with clinical studies; • vendors in connection with preclinical development activities; and • vendors related to development, manufacturing and distribution of clinical trial materials. We base our expenses related to clinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple CROs that conduct and manage clinical studies on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the clinical expense. Payments under some of these contracts depend on factors such as the successful enrollment of subjects and the completion of clinical study milestones. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period and adjust accordingly. Recent Accounting Pronouncements Refer to Note 2 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K for a discussion of recent accounting pronouncements. Results of Operations The following is a discussion of the components of results of operations. This section generally discusses 2025 and 2024 items and year-to-year comparisons between 2025 and 2024. Discussions of 2024 items and year-to-year comparisons between 2024 and 2023 that are not included in this Annual Report on Form 10-K can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” Part II, Item 7 of our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the SEC on February 11, 2025. Comparison of Years Ended December 31, 2025 and 2024 The following table summarizes our results of operations for the years ended December 31, 2025 and 2024, together with the dollar change in those items: Years Ended December 31, Period to 2025 2024 Period Change (in thousands) Revenue: Collaboration revenue $ — $ 35,000 $ (35,000 ) Grant revenue 3,510 2,314 1,196 Total revenue 3,510 37,314 (33,804 ) Operating expenses: Research and development 284,806 310,236 (25,430 ) 105 Acquired in-process research and development 96,253 — 96,253 General and administrative 73,542 72,977 565 Collaboration expense, net 213,480 120,667 92,813 Total operating expenses 668,081 503,880 164,201 Loss from operations (664,571 ) (466,566 ) (198,005 ) Other income, net 86,606 103,901 (17,295 ) Net loss before income taxes (577,965 ) (362,665 ) (215,300 ) Provision for income taxes (3,634 ) (3,587 ) (47 ) Net loss $ (581,599 ) $ (366,252 ) $ (215,347 ) Collaboration Revenue No collaboration revenue was recognized for the year ended December 31, 2025. Collaboration revenue was $35.0 million for the year ended December 31, 2024 and was related to Vertex’s achievement of a $10.0 million research milestone and $25.0 million research milestone under the Non-Ex License Agreement with Vertex in 2024. Refer to Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K for a description of revenue recognized related to Vertex. Grant Revenue Grant revenue was $3.5 million and $2.3 million, respectively, for the years ended December 31, 2025 and 2024. Research and Development Expenses Research and development expenses were $284.8 million for the year ended December 31, 2025, compared to $310.2 million for the year ended December 31, 2024. The following table summarizes our research and development expenses for the years ended December 31, 2025 and 2024, together with the changes in those items in dollars (in thousands): Years Ended December 31, Period to Period 2025 2024 Change External research and development expenses $ 76,629 $ 80,197 $ (3,568 ) Employee related expenses 63,786 76,029 (12,243 ) Facility expenses 92,381 98,003 (5,622 ) Stock-based compensation expenses 34,374 47,944 (13,570 ) Other expenses 1,225 2,019 (794 ) Sublicense and license fees 16,411 6,044 10,367 Total research and development expenses $ 284,806 $ 310,236 $ (25,430 ) The decrease of approximately $25.4 million was primarily attributable to the following: • $25.8 million of decreased employee-related expenses, including stock-based compensation expenses, primarily driven by decreased headcount; • $5.6 million of decreased facility expenses primarily driven by lower laboratory-related costs; • $3.6 million of decreased external research and development costs, primarily associated with a decrease in variable external research and manufacturing costs; offset by • $10.4 million of increased sublicense and license fees, primarily attributable to costs incurred related to a contingent liability as of December 31, 2025, as described in Note 9 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K. Acquired In-Process Research and Development Expenses Acquired in-process research and development expenses were $96.3 million for the year ended December 31, 2025. There were no acquired in-process research and development expenses for the year ended December 31, 2024. The $96.3 million acquired in-process research and development expense is attributable to the costs incurred upon entering the Sirius Agreement during the second quarter of 2025, as described in Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K. General and Administrative Expenses General and administrative expenses were $73.5 million for the year ended December 31, 2025, compared to $73.0 million for the year ended December 31, 2024. 106 Collaboration Expense, Net Collaboration expense, net, was $213.5 million for the year ended December 31, 2025, compared to $120.7 million for the year ended December 31, 2024. In 2024, we exercised our option to defer specified costs under the CASGEVY program in excess of the $110.3 million deferral limit under the A&R Vertex JDCA, as amended. The increase of approximately $92.8 million in collaboration expense, net, was primarily attributable to reaching the deferral limit in 2024, as no such limit was applicable in 2025. Absent the deferral limit, the increase was primarily attributable to an increase in our share of CASGEVY operating expenses related to increased commercial and manufacturing costs for CASGEVY when compared to the prior period, which was partially offset by an increase in our share of CASGEVY revenue. Other Income, Net Other income, net, was $86.6 million for the year ended December 31, 2025, compared to $103.9 million for the year ended December 31, 2024. The decrease in other income, net, was primarily due to a decrease in interest income earned on cash, cash equivalents and marketable securities for the year ended December 31, 2025. Liquidity and Capital Resources Sources of Liquidity We have predominantly incurred losses and cumulative negative cash flows from operations since our inception. As of December 31, 2025, we had $1,975.8 million in cash, cash equivalents and marketable securities, of which approximately $103.4 million was held outside of the United States, and an accumulated deficit of $1,947.6 million. We anticipate that we will continue to incur losses for at least the next several years. We expect to continue to incur research and development costs and general and administrative expenses, consistent with costs associated with research and development at companies of our size and stage of development, and, as a result, we will need additional capital to fund our operations, which we may raise through public or private equity or debt financings, strategic collaborations, or other sources. At-the-Market Offerings (ATM) We entered into an Open Market Sale AgreementSM, or the Sales Agreement, with Jefferies LLC under which we, at our sole discretion, are able to offer and sell, from time to time at prevailing market prices, our common shares. The following are in connection with the Sales Agreement. 2021 ATM In January 2021, we filed a prospectus supplement with the SEC to offer and sell, from time to time, common shares having aggregate gross proceeds of up to $600.0 million, or, together with the subsequent prospectus supplements filed in July 2021 and August 2024 relating to the common shares remaining under the original prospectus supplement, the 2021 ATM. In 2025, we issued and sold an aggregate of 6.1 million common shares under the 2021 ATM at an average price of $59.63 per share for aggregate proceeds of $359.0 million, which were net of equity issuance costs of $4.7 million, excluding stamp taxes of $3.6 million. In 2024, we issued and sold 0.4 million common shares under the 2021 ATM at an average price of $55.81 per share for aggregate proceeds of $21.7 million, which were net of equity issuance costs of $0.3 million, excluding stamp taxes of $0.2 million. In 2023, we issued and sold 0.5 million common shares under the 2021 ATM at an average price of $72.32 per share for aggregate proceeds of $32.7 million, which were net of equity issuance costs of $0.4 million, excluding stamp taxes of $0.3 million. As of December 31, 2025, we issued and sold an aggregate of 8.0 million common shares under the 2021 ATM at an average price of $74.77 per share for aggregate proceeds of $592.2 million, which were net of equity issuance costs of $7.8 million, excluding stamp taxes of $5.9 million. As of December 31, 2025, no common shares remain available under the 2021 ATM. 2025 ATM In October 2025, we filed a new prospectus supplement with the SEC to offer and sell, from time to time, common shares having aggregate gross proceeds of up to $600.0 million, referred to herein as the 2025 ATM. In 2025, we issued and sold an aggregate of 0.7 million common shares under the 2025 ATM at an average price of $60.81 per share for aggregate proceeds of $42.3 million, which were net of equity issuance costs of $0.5 million, excluding stamp taxes of $0.4 million. Common shares having aggregate gross proceeds up to $557.2 million remain available under the 2025 ATM. Share Issuance Agreement with Sirius Therapeutics As described in Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K, we and Sirius entered into a share issuance agreement and we registered and issued 1,842,105 common shares to Sirius, nominal value CHF 0.03 per share, at an issue price of $38.00 per share as partial consideration for entering into the Sirius Agreement. 107 Additional Financings In February 2024, we entered into an investment agreement for the sale of approximately $280.0 million of our common shares to a group of institutional investors in a registered direct offering, at a price per share of $71.50. We received net proceeds of $279.0 million, excluding stamp taxes due of $2.8 million. Sources of Liquidity Cash Flows Discussions of 2024 items and year-to-year comparisons between 2024 and 2023 that are not included in this Annual Report on Form 10-K can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” Part II, Item 7 of our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the SEC on February 11, 2025. The following table provides information regarding our cash flows for each of the periods below: Years Ended December 31, 2025 2024 (in thousands) Net cash used in operating activities $ (345,014 ) $ (142,774 ) Net cash used in investing activities (31,805 ) (280,481 ) Net cash provided by financing activities 426,026 331,984 Effect of exchange rate changes on cash 95 (21 ) Increase (decrease) in cash and restricted cash $ 49,302 $ (91,292 ) Operating Activities Net cash used in operating activities was $345.0 million for the year ended December 31, 2025, compared to net cash used in operating activities of $142.8 million for the year ended December 31, 2024. The $202.2 million increase in cash used in operating activities was primarily driven by the timing of receipt of milestone payments from Vertex which were recorded in accounts receivable as of the respective year-end periods and paid in the subsequent year ($200.0 million paid in the first quarter of 2024 compared to $25.0 million paid in the first quarter of 2025). Investing Activities Net cash used in investing activities for the year ended December 31, 2025 was $31.8 million, compared to net cash used in investing of $280.5 million for the year ended December 31, 2024. The decrease in net cash used in investing activities was primarily a result of the net purchase position for marketable debt securities for the year ended December 31, 2024, compared to a net maturity position for marketable debt securities for the year ended December 31, 2025. Financing Activities Net cash provided by financing activities for the year ended December 31, 2025 was $426.0 million, compared to net cash provided by financing of $332.0 million for the year ended December 31, 2024. Net cash provided by financing activities for the year ended December 31, 2025 consisted primarily of net proceeds of approximately $397.3 million from the sale of common shares issued in connection with our 2021 ATM and 2025 ATM, in the aggregate, as well as net proceeds of approximately $27.7 million from stock option exercise proceeds. Net cash provided by financing activities for the year ended December 31, 2024 primarily consisted of net proceeds of approximately $279.0 million from the issuance of common shares in connection with our registered direct offering, net proceeds of approximately $31.2 million from stock option exercises, and net proceeds of approximately $21.7 million from the issuance of common shares in connection with our 2021 ATM. Funding Requirements Our primary uses of capital are, and we expect will continue to be, research and development activities, manufacturing activities, compensation and related expenses, laboratory and related supplies, legal and other regulatory expenses, patent prosecution filing, defense and intellectual property maintenance costs, business development activities and general overhead costs, including costs associated with operating as a public company. We expect to continue to incur operating expenses consistent with costs associated with research and development at companies of our size and stage of development, which may increase in the future to support continued research and development activities and potential commercialization of our product candidates. Although we and our partner, Vertex, have received marketing approvals for CASGEVY in certain jurisdictions, we cannot guarantee we and Vertex will receive additional marketing approvals for CASGEVY or we will receive marketing approvals for our other product candidates in the future. Most of our programs are still in early stages of research and development and the outcome of our efforts is uncertain, and we cannot estimate the actual amounts necessary to successfully complete the development, manufacture and commercialization of any current or future product candidates, if approved, or whether, or when, we may achieve profitability. 108 Until such time as we can generate substantial product revenues, if ever, we expect to finance our cash needs through a combination of equity financings, debt financings and payments received in connection with our collaboration and license agreements. We intend to consider opportunities to raise additional funds through the sale of equity or debt securities when market conditions are favorable to us to do so. However, the trading prices for our common shares and other biopharmaceutical companies have been highly volatile. As a result, we may face difficulties raising capital through sales of our common shares or such sales may be on unfavorable terms. In addition, a recession, depression or other sustained adverse market event, including resulting from the uncertain geopolitical environment, global trade policy and global economic conditions, could materially and adversely affect our business and the value of our common shares. To the extent that we raise additional capital through the future sale of equity or debt securities, the ownership interests of our shareholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing shareholders. If we raise additional funds through license or collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. Outlook Based on our research and development plans and our timing expectations related to the progress of our programs, we expect our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditures for at least the next 24 months without giving effect to any additional proceeds we may receive under our license agreements and collaborations, including with Vertex, and any other capital raising transactions we may complete. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect. Given our need for additional financing to support the long-term clinical development and future commercialization of our programs, as applicable, we intend to consider additional financing opportunities when market terms are favorable to us. Our ability to generate revenue and achieve profitability depends significantly on our success in many areas, including: developing our delivery technologies and our gene editing technology platform; selecting appropriate product candidates to develop; completing research and preclinical and clinical development of selected product candidates; obtaining regulatory approvals and marketing authorizations for product candidates for which we complete clinical trials; developing a sustainable and scalable manufacturing process for product candidates; launching and commercializing product candidates for which we obtain regulatory approvals and marketing authorizations, either directly or with a collaborator or distributor; obtaining market acceptance of our product candidates, either directly or with a collaborator or distributor, if approved, including for CASGEVY; addressing any competing technological and market developments; negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter; maintaining good relationships with our collaborators and licensors; maintaining, defending, protecting and expanding our estate of intellectual property rights, including patents, trade secrets and know-how; and attracting, hiring and retaining qualified personnel. Contractual and Other Obligations Operating lease and sublease obligations Our operating lease obligations primarily consist of lease payments on our office and laboratory facility in Boston, Massachusetts, as well as lease payments on our cell manufacturing facility in Framingham, Massachusetts, which are described in further detail in Note 7 of our consolidated financial statements included in this Annual Report on Form 10-K. Future contractual payments on operating lease and sublease obligations due within one year of December 31, 2025 are $29.7 million, and future contractual payments on operating lease and sublease obligations due greater than one year from December 31, 2025 are $235.9 million. Other obligations Under the A&R Vertex JDCA, as amended, for 2022, 2023 and 2024, the Company had an option to defer a portion of its share of costs if spending on the CASGEVY program exceeded specified amounts, which the Company exercised in each such year, resulting in deferred costs of $221.8 million, in the aggregate. Any deferred amounts are only payable to Vertex as an offset against future profitability of the CASGEVY program and the amounts payable are capped at a specified maximum amount per year. Deferred costs associated with the CASGEVY program have not been recognized as of December 31, 2025 because a reasonable estimate of future payments against future profitability cannot be made. In the normal course of business, we enter into agreements with CROs for clinical trials and clinical supply manufacturing and with vendors for preclinical research studies and other services and products for operating purposes. These contracts are generally cancelable at any time by us upon less than 180 days’ prior written notice. Certain of these agreements require us to pay milestones to such third parties upon achievement of certain development, regulatory or commercial milestones as further described in Note 9 of our consolidated financial statements included in this Annual Report on Form 10-K. Amounts related to contingent milestone payments are not considered contractual obligations as they are contingent on the successful achievement of certain development, regulatory 109 approval and commercial milestones, which may not be achieved. We also have obligations to make future payments to third parties that become due and payable on the achievement of certain milestones, including future payments to third parties with whom we have entered into research, development and commercialization agreements. We have not included these commitments on our balance sheet because the achievement and timing of these milestones is not fixed and determinable.