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What changed in Intellia Therapeutics, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Intellia Therapeutics, Inc.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+725 added−885 removedSource: 10-K (2025-02-27) vs 10-K (2024-02-22)

Top changes in Intellia Therapeutics, Inc.'s 2024 10-K

725 paragraphs added · 885 removed · 302 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

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Biggest changeUnder this agreement, we also may access the Regeneron Genetics Center and proprietary mouse models to be provided by Regeneron for a limited number of our liver programs. 15 We amended the 2016 Regeneron Agreement in May 2020 to, among other things, (a) extend the technology collaboration, and related target selection rights, until April 2024, which Regeneron has since further extended to April 2026; (b) increase the number of exclusive in vivo targets to which Regeneron may develop CRISPR/Cas-based therapeutic products to fifteen; and (c) grant Regeneron a non-exclusive license under certain of our IP to independently develop and commercialize up to 10 CRISPR/Cas-based ex vivo gene edited products made using certain defined cell types.
Biggest changeThe 2020 Regeneron Amendment also granted Regeneron exclusive rights to develop products for five additional in vivo CRISPR/Cas-based therapeutic liver targets and non-exclusive rights to independently develop and commercialize up to 10 ex vivo gene edited products made using certain defined cell types.
The 2016 Regeneron Agreement has two principal components: (i) a product development component under which the parties will research, develop and commercialize CRISPR/Cas-based therapeutic products primarily focused on genome editing in the liver, and (ii) a technology collaboration component, pursuant to which we and Regeneron will engage in research-related activities aimed at discovering and developing novel technologies and improvements to CRISPR/Cas technology to enhance our genome editing platform.
The 2016 Regeneron Agreement has two principal components: i) a product development component under which the parties will research, develop and commercialize CRISPR/Cas-based therapeutic products primarily focused on genome editing in the liver, and ii) a technology collaboration component, pursuant to which the Company and Regeneron will engage in research-related activities aimed at discovering and developing novel technologies and improvements to CRISPR/Cas technology to enhance the Company’s genome editing platform.
In October 2023, Regeneron notified us that it was exercising its one-time option to extend the technology collaboration term for an additional two years (the “2024 Technology Collaboration Extension”), until April 2026, in exchange for a nonrefundable payment of $30.0 million due in April 2024.
In October 2023, Regeneron notified the Company that it was exercising its one-time option to extend the Technology Collaboration Term for an additional two years (the “2024 Technology Collaboration Extension”) , until April 2026 , in exchange for a nonrefundable payment of $ 30.0 million that was paid in April 2024. 2024 Technology Collaboration Extension: Accounting Analysis.
To fully realize the transformative potential of CRISPR/Cas9-based technologies, we are building a full-spectrum gene editing company, by leveraging our modular platform, to advance in vivo and ex vivo therapies for diseases with high unmet need by pursuing two primary approaches. For in vivo applications to address genetic diseases, we deploy CRISPR/Cas9 as the therapy.
To fully realize the transformative potential of CRISPR-based technologies, the Company is building a full-spectrum gene editing company, by leveraging its modular platform, to advance in vivo and ex vivo therapies for diseases with high unmet need by pursuing two primary approaches. For in vivo applications to address genetic diseases, the Company deploys CRISPR as the therapy.
SparingVision SAS (“SparingVision”) In October 2021, we entered into a license and collaboration agreement with SparingVision, a genomic medicine company developing vision saving treatments for ocular diseases, to develop novel genomic medicines utilizing CRISPR/Cas9 technology for the treatment of ocular diseases.
F- 22 SparingVision SAS In October 2021, the Company and SparingVision, a genomic medicine company developing vision saving treatments for ocular diseases, entered into a license and collaboration agreement (the “SparingVision LCA”) to develop novel genomic medicines utilizing CRISPR/Cas9 technology for the treatment of ocular diseases.
In September 2023, we further amended the 2016 Regeneron Agreement (the “2023 Regeneron Amendment”) to expand the research and development collaboration to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases.
In September 2023, Regeneron and Intellia further expanded the research collaboration (the “2023 Regeneron Amendment”) to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases.
Our in vivo programs use CRISPR/Cas9 to enable precise editing of disease-causing genes directly inside the human body. In addition, we are advancing ex vivo applications to address immuno-oncology and autoimmune diseases, where we use CRISPR/Cas9 as the tool to create the engineered cell therapy. For our ex vivo programs, CRISPR/Cas9 is used to engineer human cells outside the body.
The Company’s in vivo programs use CRISPR to enable precise editing of disease-causing genes directly inside the human body. In addition, the Company is advancing ex vivo applications to address immuno-oncology and autoimmune diseases, where it uses CRISPR as the tool to create the engineered cell therapy.
We granted SparingVision exclusive rights to our proprietary in vivo CRISPR/Cas9-based genome editing technology for up to three ocular targets addressing diseases with significant unmet medical need. In addition, the parties are collaborating to research and develop novel self-inactivating AAV vectors and LNP-based product candidates to address delivery of CRISPR/Cas9 genome editing reagents to the retina.
The Company granted SparingVision exclusive rights to its proprietary in vivo CRISPR/Cas9-based genome editing technology for up to three ocular targets addressing diseases with significant unmet medical need. In addition, the parties will research and develop novel self-inactivating adeno-associated virus (“AAV”) vectors and lipid nanoparticle (“LNP”)-based approaches to address delivery of CRISPR/Cas9 genome editing reagents to the retina.
Collaborations and Other Arrangements To accelerate the development and commercialization of CRISPR/Cas9-based products in multiple therapeutic areas, we have formed, and intend to seek other opportunities to form, strategic alliances with collaborators who can augment our leadership in CRISPR/Cas9 therapeutic development. Regeneron Pharmaceuticals, Inc.
Collaborations and Other Arrangements To accelerate the development and commercialization of gene editing products in multiple therapeutic areas, the Company has formed, and intends to seek other opportunities to form, strategic alliances with collaborators who can augment its leadership in CRISPR/Cas9 therapeutic development.
SparingVision will lead and fund the preclinical and clinical development for the genome editing product candidates pursued under the collaboration. We will also be eligible to receive certain research, development and commercial milestone cash payments (up to approximately $200.0 million per product) as well as royalties on 16 potential future sales of products arising from the collaboration.
The Company will also be eligible to receive certain research, development and commercial milestone payments (up to approximately $ 200.0 million per product) as well as royalties on potential future sales of products arising from the collaboration. SparingVision LCA: Accounting Analysis. The Company determined that the accounting for the SparingVision LCA is within the scope of ASC 606.
(“Regeneron”) In April 2016, we entered into a license and collaboration agreement with Regeneron (as amended from time to time, the “2016 Regeneron Agreement”).
As such, no costs to obtain or fulfill a contract have been capitalized in any period. Regeneron Pharmaceuticals, Inc. In April 2016, the Company entered into a license and collaboration agreement with Regeneron (as amended from time to time, the “2016 Regeneron Agreement”).
Our deep scientific, technical and clinical development experience, along with our robust intellectual property (“IP”) portfolio, have enabled us to unlock broad therapeutic applications of CRISPR/ Cas9 and related technologies to create new classes of genetic medicine. Treating—and potentially curing—a broad range of severe diseases will require multiple gene editing approaches.
For its ex vivo programs, CRISPR is used to engineer human cells outside the body. The Company’s deep scientific, technical and clinical development experience, along with its robust intellectual property (“IP”) portfolio, have enabled it to unlock broad therapeutic applications of CRISPR and related technologies to create new classes of genetic medicine.
The expanded research and development collaboration will leverage our proprietary Nme2 CRISPR/Cas9 genome editing systems adapted for viral vector delivery and designed to precisely modify a target gene and Regeneron’s proprietary antibody-targeted AAV vectors and delivery systems.
The collaboration will leverage Intellia’s proprietary Nme2 CRISPR/Cas9 genome editing systems adapted for viral vector delivery and designed to precisely modify a target gene and Regeneron’s proprietary antibody-targeted adeno-associated virus vectors and delivery systems; each party will have the opportunity to lead potential development and commercialization for one product candidate, and the party that is not leading development and commercialization will have the option to enter into a co-development and co-promotion agreement for the target. 2023 Regeneron Amendment: Accounting Analysis .
Invention Management Agreement On December 15, 2016, we entered into a Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement (the “Invention Management Agreement”), with UC, Vienna, Dr. Charpentier, Caribou, CRISPR Therapeutics AG, ERS Genomics Ltd. and TRACR Hematology Ltd. Under the Invention Management Agreement, Dr.
(3) 10.13# Form of Employment Agreement for Executive Officers (14) 10.14† Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement dated December 15, 2016 by and between the Registrant, CRISPR Therapeutics AG, The Regents of the University of California, University of Vienna, ERS Genomics Ltd., TRACR Hematology Ltd., Caribou Biosciences, Inc., and Dr.
(“ReCode”) On February 15, 2024, we announced a strategic collaboration with ReCode Therapeutics, Inc. (“ReCode”), a clinical-stage genetic medicines company, to develop novel genomic medicines for the treatment of cystic fibrosis (“CF”). CF is a genetic disease caused by mutations in the CFTR gene, leading to the accumulation of thick mucus in the lungs, 17 digestive systems and other organs.
(“ReCode”) On February 14, 2024, the Company entered into a license, collaboration and option agreement with ReCode (the “ReCode LCA”), a clinical-stage genetic medicines company, to develop novel genomic medicines for the treatment of cystic fibrosis (“CF”).
We also have entered into three co-development and co-funding agreements with Regeneron, specifically the ATTR Co/Co and co-development and co-funding agreements for the treatment of hemophilia A and hemophilia B (the “Hemophilia Co/Co”) agreements.
In May 2020, the Company entered into (i) amendment no. 1 (the “2020 Regeneron Amendment”) to the 2016 Regeneron Agreement, (ii) co-development and co-funding agreements for the treatment of hemophilia A and hemophilia B (the “Hemophilia Co/Co”) agreements and (iii) a stock purchase agreement.
We will have an option to obtain exclusive U.S. commercialization rights for product candidates arising from two of three collaboration targets. Refer to Notes 9 and 10 to our consolidated financial statements of this Annual Report on Form 10-K for additional information related to the terms of the agreement between us and SparingVision. Kyverna Therapeutics, Inc.
SparingVision will lead and fund the preclinical and clinical development for the genome editing product candidates pursued under the collaboration. The Company will have an option to obtain exclusive U.S. commercialization rights for product candidates arising from two of three collaboration targets.
We will be eligible to receive up to $184.0 million per product in development and commercial milestone payments, as well as up to mid-single-digit royalties on potential future sales. In addition, the agreement grants us options to co-develop and co-commercialize up to two products worldwide with rights to lead commercialization in the U.S.
The Company will be eligible to receive pre-specified development and commercial milestone payments, up to $ 262.0 million per product, as well as single digit F- 23 royalties on potential sales. Certain milestone and royalty payments may be removed or reduced for a product if the Company exercises the Co/Co option.
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Item 1. Business Overview We are a leading clinical-stage gene editing company, focused on developing potentially curative therapeutics using CRISPR/Cas9-based technologies.
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Item 1. Financi al Statements INTELLIA THERAPEUTICS, INC.
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CRISPR/Cas9, an acronym for C lustered, R egularly I nterspaced S hort P alindromic R epeats (“CRISPR”)/ C RISPR a ssociated 9 (“Cas9”), is a technology for genome editing, the process of altering selected sequences of genomic deoxyribonucleic acid (“DNA”).
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CONSOLIDATED BALANCE SHEETS (Amounts in thousands except share and per share data) December 31, 2024 December 31, 2023 ASSETS Current assets: Cash and cash equivalents $ 189,182 $ 226,748 Marketable securities 412,333 685,475 Accounts receivable 8,517 36,456 Prepaid expenses and other current assets 29,831 49,651 Total current assets 639,863 998,330 Marketable securities - noncurrent 260,215 99,864 Property and equipment, net 27,381 32,760 Operating lease right-of-use assets 219,292 115,375 Equity method investment - 11,765 Investments and other assets 44,264 42,883 Total assets $ 1,191,015 $ 1,300,977 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 14,589 $ 7,452 Accrued expenses 55,355 67,017 Current portion of operating lease liability 20,246 18,599 Current portion of deferred revenue 20,661 22,140 Total current liabilities 110,851 115,208 Deferred revenue, net of current portion 18,256 38,853 Long-term operating lease liability 189,952 96,747 Total liabilities 319,059 250,808 Commitments and contingencies (Note 8) Stockholders’ equity: Common stock, $ 0.0001 par value; 240,000,000 shares authorized at December 31, 2024 and December 31, 2023; 102,029,594 and 92,997,158 shares issued and outstanding at December 31, 2024 and December 31, 2023, respectively 10 9 Additional paid-in capital 3,048,741 2,710,797 Accumulated other comprehensive income (loss) 605 ( 2,258 ) Accumulated deficit ( 2,177,400 ) ( 1,658,379 ) Total stockholders’ equity 871,956 1,050,169 Total liabilities and stockholders’ equity $ 1,191,015 $ 1,300,977 The accompanying notes are an integral part of these consolidated financial statements.
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With proprietary CRISPR/Cas9-based technology at the core of our platform, we continue to add new capabilities to expand our current solutions for addressing a multitude of life-threatening diseases. These additions include our proprietary base editor and DNA writing technology, as well as novel CRISPR enzymes, which provide us with the capabilities to achieve multiple editing strategies.
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CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Amounts in thousands except per share data) Year Ended December 31, 2024 2023 2022 Collaboration revenue $ 57,877 $ 36,275 $ 52,121 Operating expenses: Research and development 466,311 435,069 419,979 General and administrative 125,829 116,497 90,306 Total operating expenses 592,140 551,566 510,285 Operating loss ( 534,263 ) ( 515,291 ) ( 458,164 ) Other income (expense), net: Interest income 47,807 49,832 8,542 Change in fair value of investments, net ( 32,565 ) - - Loss from equity method investment - ( 15,633 ) ( 11,079 ) Change in fair value of contingent consideration - ( 100 ) ( 13,485 ) Total other income (expense), net 15,242 34,099 ( 16,022 ) Net loss $ ( 519,021 ) $ ( 481,192 ) $ ( 474,186 ) Net loss per share, basic and diluted $ ( 5.25 ) $ ( 5.42 ) $ ( 6.16 ) Weighted average shares outstanding, basic and diluted 98,849 88,770 76,972 Other comprehensive loss: Unrealized gain (loss) on marketable securities 731 3,635 ( 1,637 ) Other comprehensive gain (loss) from equity method investment - 1,568 ( 3,192 ) Comprehensive loss $ ( 518,290 ) $ ( 475,989 ) $ ( 479,015 ) The accompanying notes are an integral part of these consolidated financial statements.
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We continue to advance our platform’s modular solutions and research efforts on genome editing technologies as well as delivery and cell engineering capabilities to generate additional development candidates. Our mission is to transform the lives of people with severe diseases by developing potentially curative genome editing treatments.
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CONSOLIDATED S T ATEMENTS OF STOCKHOLDERS’ EQUITY (Amounts in thousands, except share data) Accumulated Additional Other Total Common Paid-In Comprehensive Accumulated Stockholders’ Shares Amount Capital Income (Loss) Deficit Equity Balance at December 31, 2021 74,485,883 $ 7 $ 1,745,870 $ ( 2,632 ) $ ( 703,001 ) $ 1,040,244 Issuance of common stock through follow-on offerings, net of issuance costs of $ 253 7,532,751 1 337,891 - - 337,892 Issuance of common stock through at-the-market offerings, net of issuance costs of $ 164 - 2019 Sale Agreement 579,788 1 38,885 - - 38,886 Issuance of common stock through at-the-market offerings, net of issuance costs of $ 125 - 2022 Sale Agreement 3,395,339 - 189,011 - - 189,011 Exercise of stock options 883,954 - 14,517 - - 14,517 Vesting of restricted stock units 147,674 - - - - - Issuance of shares under employee stock purchase plan 77,618 - 2,649 - - 2,649 Stock-based compensation - - 91,400 - - 91,400 Other comprehensive income (loss) - unrealized loss on marketable securities - - - ( 1,637 ) - ( 1,637 ) Other comprehensive income (loss) - unrealized loss on equity method investment - - - ( 3,192 ) - ( 3,192 ) Net loss - - - - ( 474,186 ) ( 474,186 ) Balance at December 31, 2022 87,103,007 9 2,420,223 ( 7,461 ) ( 1,177,187 ) 1,235,584 Issuance of common stock through at-the-market offerings, net of issuance costs of $ 376 - 2022 Sale Agreement 4,122,824 - 121,870 - - 121,870 Contingent consideration paid to Rewrite Holders 567,045 - 24,126 - - 24,126 Exercise of stock options 385,130 - 6,599 - - 6,599 Vesting of restricted stock units 677,055 - - - - - Issuance of shares under employee stock purchase plan 142,097 - 3,929 - - 3,929 Stock-based compensation - - 134,050 - - 134,050 Other comprehensive income (loss) - unrealized gain on marketable securities - - - 3,635 - 3,635 Other comprehensive income (loss) - unrealized gain on equity method investment - - - 1,568 - 1,568 Net loss - - - - ( 481,192 ) ( 481,192 ) Balance at December 31, 2023 92,997,158 9 2,710,797 ( 2,258 ) ( 1,658,379 ) 1,050,169 Issuance of common stock through at-the-market offerings, net of issuance costs of $ 254 - 2022 Sale Agreement 7,004,370 1 174,823 - - 174,824 Exercise of stock options 373,807 - 5,862 - - 5,862 Vesting of restricted stock units 1,433,669 - - - - - Issuance of shares under employee stock purchase plan 220,590 - 2,986 - - 2,986 Stock-based compensation - - 154,273 - - 154,273 Other comprehensive income (loss) - unrealized gain on marketable securities - - - 731 - 731 Reclassification of other comprehensive income (loss) - equity method investment - - - 2,132 - 2,132 Net loss - - - - ( 519,021 ) ( 519,021 ) Balance at December 31, 2024 102,029,594 $ 10 $ 3,048,741 $ 605 $ ( 2,177,400 ) $ 871,956 The accompanying notes are an integral part of these consolidated financial statements.
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We believe we can deliver on our mission and provide long-term benefits for all of our stakeholders by focusing on four key elements: • Develop potentially curative CRISPR/Cas9-based medicines; • Advance our science; • Be the best place to make therapies; and • Focus on long-term sustainability.
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CONSOLIDATED STATEMENTS O F CASH FLOWS (Amounts in thousands) Year Ended December 31, 2024 2023 2022 CASH FLOWS FROM OPERATING ACTIVITIES: Net loss $ ( 519,021 ) $ ( 481,192 ) $ ( 474,186 ) Adjustments to reconcile net loss to net cash used in operating activities: Depreciation and amortization 10,285 8,976 7,572 (Gain) loss on disposal of property and equipment ( 76 ) 72 ( 162 ) Stock-based compensation 154,273 134,050 91,400 (Accretion) amortization of investment discounts and premiums ( 17,817 ) ( 25,897 ) 4,003 (Recognition) deferral of equity method investment intra-entity profit on sales ( 20,967 ) 6,624 11,405 Change in fair value of investments, net 32,565 - - Loss from equity method investment - 15,633 11,079 Change in fair value of contingent consideration - 100 13,485 In-process research and development expense - - 55,990 Changes in operating assets and liabilities: Accounts receivable 27,939 ( 32,688 ) ( 1,737 ) Prepaid expenses and other current assets 5,184 ( 27,168 ) ( 2,160 ) Operating lease right-of-use assets 21,466 19,011 13,121 Other assets 917 ( 707 ) ( 1,091 ) Accounts payable 6,800 2,522 ( 4,584 ) Accrued expenses ( 10,383 ) 6,024 15,924 Deferred revenue ( 22,076 ) ( 2,778 ) ( 63,464 ) Operating lease liabilities ( 17,969 ) ( 16,668 ) ( 9,882 ) Net cash used in operating activities ( 348,880 ) ( 394,086 ) ( 333,287 ) CASH FLOWS FROM INVESTING ACTIVITIES: Purchases of property and equipment ( 5,778 ) ( 13,985 ) ( 13,558 ) Purchases of marketable securities ( 935,573 ) ( 904,464 ) ( 429,032 ) Sales and maturities of marketable securities 1,066,918 887,102 647,581 Proceeds from sale of property and equipment - - 150 Acquired in-process research and development, net of cash acquired of $ 287 - - ( 44,832 ) Net cash provided by (used in) investing activities 125,567 ( 31,347 ) 160,309 CASH FLOWS FROM FINANCING ACTIVITIES: Net proceeds from issuance of common stock through follow-on offerings, net of issuance costs - - 337,892 Net proceeds from issuance of common stock through at-the-market offerings 176,899 119,795 227,897 Proceeds from options exercised 5,862 6,599 14,517 Issuance of shares through employee stock purchase plan 2,986 3,929 2,649 Net cash provided by financing activities 185,747 130,323 582,955 Net (decrease) increase in cash, cash equivalents and restricted cash equivalents ( 37,566 ) ( 295,110 ) 409,977 Cash, cash equivalents and restricted cash equivalents, beginning of period 240,353 535,463 125,486 Cash, cash equivalents and restricted cash equivalents, end of period $ 202,787 $ 240,353 $ 535,463 Reconciliation of cash, cash equivalents and restricted cash equivalents to consolidated balance sheet: Cash and cash equivalents $ 189,182 $ 226,748 $ 523,506 Restricted cash equivalents, included in investments and other assets 13,605 13,605 11,957 Total cash, cash equivalents and restricted cash equivalents $ 202,787 $ 240,353 $ 535,463 SUPPLEMENTAL DISCLOSURES OF CASH FLOW INFORMATION: Purchases of property and equipment unpaid at period end $ 577 $ 1,525 $ 1,623 Operating lease liability arising from obtaining right-of-use assets 112,821 1,311 67,053 Non-cash trade-in of property and equipment 99 - 200 Proceeds from at-the-market offerings unpaid at period end - 2,075 - Shares issued for Rewrite contingent consideration - 24,126 - Contingent consideration liability assumed in asset acquisition - - 10,541 The accompanying notes are an integral part of these consolidated financial statements.
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Our lead in vivo candidates, NTLA-2001 for the treatment of transthyretin (“ATTR”) amyloidosis and NTLA-2002 for the treatment of hereditary angioedema (“HAE”), are the first CRISPR/Cas9-based therapy candidates to be administered systemically, via intravenous (“IV”) infusion, for precision editing of a gene in a target tissue in humans.
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F- 6 INTELLIA THERAPEUTICS, INC. NOTES TO CONSOLIDATED FINANCIAL STATEMENTS 1. Nature of Operations Organization Intellia Therapeutics, Inc. (“Intellia” or the “Company”) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies.
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In addition, we are advancing multiple ex vivo programs, wholly owned and in collaboration with partners, for the treatment of immuno-oncology and autoimmune diseases. CRISPR/Cas9 Technology The Nobel Prize-winning CRISPR/Cas9 system developed by one of our scientific co-founders, Dr.
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CRISPR is a gene editing technology which is also sometimes referred to as CRISPR/Cas or CRISPR/Cas9 when referring to the use of CRISPR technology with the Cas9 enzyme. Since its inception, Intellia has focused on leveraging gene editing technology to develop novel, first-in-class medicines that address important unmet medical needs and advance the treatment paradigm for patients.
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Jennifer Doudna, and her collaborators, offers a revolutionary approach for therapeutic development due to its broad ability to precisely edit the genome. This system can be used to make three general types of edits: knockouts, repairs and insertions.
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Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies.
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Each of these editing strategies takes advantage of the Cas9 endonuclease, an enzyme which can be programmed to edit double-stranded DNA at specific locations using a ribonucleic acid (“RNA”) molecule, called a guide RNA (“gRNA”). The desired edits result from naturally-occurring biological mechanisms that effect particular types of genetic alterations.
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The Company was founded and commenced operations in 2014.
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CRISPR/Cas9 genome editing has the potential to make permanent, precisely targeted changes in a patient’s chromosomes and repair the underlying genetic mutation, whereas more traditional gene therapy typically involves introducing a non-permanent copy of a gene into a patient’s cells. 6 Strategy Our strategy is to advance our full-spectrum gene editing company, focused on developing and commercializing curative CRISPR/Cas9-based therapeutics, by leveraging our modular platforms.
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The Company is subject to risks and uncertainties common to clinical-stage companies in the biotechnology industry, including, but not limited to, development by competitors of more advanced or effective therapies, dependence on key executives, protection of and dependence on proprietary technology, compliance with government regulations and ability to secure additional capital to fund operations.
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Our approach to realizing the broad potential of genome editing includes: Focusing on Indications that Enable Us to Fully Develop the Potential of the CRISPR/Cas9 System.
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Programs currently in development or moving into development will require significant additional research and development efforts, including preclinical and clinical testing and regulatory approval prior to commercialization. These efforts require significant amounts of additional capital, adequate personnel and infrastructure and extensive compliance-reporting capabilities.
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To maximize our opportunity to rapidly develop clinically successful products, we have applied a risk-mitigated approach to selecting indications with significant unmet medical needs based on four primary criteria: • the type of edit: knockout, repair or insertion; • the delivery modality for in vivo and ex vivo applications; • the existence of efficient regulatory pathways to approval; and • the potential for the CRISPR/Cas9 system to provide improved therapeutic benefits over existing therapeutic options.
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Even if the Company’s product development efforts are successful, it is uncertain when, if ever, the Company will realize significant revenue from product sales.
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We believe these selection criteria position us to build a diversified pipeline, in which we are not reliant on any single delivery technology or editing approach for success. This approach has the potential to increase the probabilities of success in our initial indications and generate insights that will accelerate the development of additional therapeutic products.
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Liquidity Since its inception through December 31, 2024, the Company has funded its operations through its initial public offering (“IPO”) and concurrent private placements, follow-on public offerings, at-the-market offerings and the sale of convertible preferred stock, as well as through its collaboration agreements.
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Specifically, we believe we can apply the learnings from our current programs to inform our selection of additional indications and targets of interest. Aggressively Pursuing In Vivo Liver Indications to Develop Therapeutics with Our Proprietary Delivery System.
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The Company expects that its cash, cash equivalents and marketable securities as of December 31, 2024 will enable the Company to fund its ongoing operating expenses and capital expenditure requirements for at least the twelve-month period following the issuance of these consolidated financial statements. 2.
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For our in vivo indications, we select well-validated targets in diseases with significant unmet medical needs where there are predictive biomarkers, or measurable indicators of a biological condition or state, with strong disease correlation and where the CRISPR/Cas9 technology and our proprietary delivery tools can be applied towards developing novel therapeutics.
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Summary of Significant Accounting Policies Basis of Presentation The consolidated financial statements include the accounts of Intellia Therapeutics, Inc. and its wholly owned, controlled subsidiary, Intellia Securities Corp. All intercompany balances and transactions have been eliminated in consolidation.
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Our current in vivo pipeline targets diseases of the liver. Our two lead clinical programs in development aim to treat ATTR amyloidosis and HAE. Both programs utilize our proprietary lipid nanoparticle (“LNP”) delivery system to knockout a target gene to halt production of an unwanted protein.
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Comprehensive loss is comprised of net loss, unrealized gain (loss) on marketable securities and other comprehensive gain (loss) from equity method investment . Use of Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States of America (“U.S.
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In addition, we are developing therapeutic candidates that leverage our modular gene insertion platform to restore native protein for the treatment of the lung manifestation of alpha-1 antitrypsin deficiency (“AATD”), hemophilia A, hemophilia B, and additional disease indications. Progressing Ex Vivo Therapeutic Programs. We are independently researching proprietary engineered cell therapies to treat various cancers and autoimmune diseases.
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GAAP”) requires management to make estimates, judgments and assumptions that affect the amounts reported in the financial statements and accompanying notes. Significant estimates in these consolidated financial statements have been made in connection with the calculation of revenues, research and development expenses, valuation and determination of impairment of equity and fair value method investments, contingent consideration and stock-based compensation expense.
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We are deploying our LNP-based cell engineering platform and allogeneic technology, a first-of-its-kind engineering solution designed to avoid both T cell and natural killer (“NK”) cell-mediated rejection, to advance a pipeline of wholly owned and partnered ex vivo programs.
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The Company bases its estimates on historical experience and various other assumptions that management believes to be reasonable under the circumstances at the time such estimates are made. Actual results could differ from those estimates. The Company periodically reviews its estimates in light of changes in circumstances, facts and experience.
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We are pursuing targeting modalities, such as T cell receptors (“TCRs”) and chimeric antigen receptors (“CARs”), with broad potential in multiple immuno-oncology and autoimmune indications. Continuing to Leverage Strategic Partnerships to Accelerate Clinical Development. We view strategic partnerships as important drivers for accelerating the achievement of our goal of rapidly developing potentially curative therapies.
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F- 7 The effects of material revisions in estimates are reflected in the consolidated financial statements prospectively from the date of the change in estimate. Fair Value Measurements The Company’s financial instruments include cash equivalents, restricted cash equivalents, marketable securities, accounts receivable, non-marketable securities, accounts payable and accrued expenses.
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The potential application of the CRISPR/Cas9 system and derivative technologies is extremely broad, and we plan to continue to identify partners who can contribute meaningful resources and technical expertise to our programs and allow us to more rapidly bring scientific innovation to a broader patient population. For example, we continue to collaborate on in vivo programs with Regeneron Pharmaceuticals, Inc.
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Certain of the Company’s financial assets, including cash equivalents, restricted cash equivalents and marketable securities, have been initially valued at the transaction price, and subsequently revalued at the end of each reporting period, utilizing third party pricing services or other observable market data. The pricing services utilize industry standard valuation models and observable market inputs to determine value.
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(“Regeneron”), a leader in genetics-driven drug discovery and development, and to advance our collaborations with AvenCell Therapeutics, Inc. (“AvenCell”), a company with a world-leading clinical-stage universal chimeric antigen receptor T (“CAR-T”) cell platform; SparingVision SAS (“SparingVision”), a genomic medicine company developing vision saving treatments for ocular diseases; Kyverna Therapeutics, Inc.
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Investments in non-marketable securities are accounted for using the measurement alternative at cost minus impairment, adjusted for changes in observable prices. Refer to Note 4 for further information regarding the Company’s fair value measurements.
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(“Kyverna”), a cell therapy company engineering a new class of therapies for autoimmune and inflammatory diseases; and ONK Therapeutics, Ltd. (“ONK”), a cell therapy company engineering a new class of NK cell therapies to treat cancer. 7 Growing Our Leadership Position in the Field of Genome Editing.
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Other financial instruments, including accounts receivable, accounts payable and accrued expenses, are carried at cost, which approximate fair value due to the short duration and term to maturity. Cash Equivalents The Company considers all highly liquid investments with maturities of three months or less when purchased to be cash equivalents.
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We believe we have built the broadest and deepest gene editing toolbox, which enables us to select the best tools for each therapeutic application. We continue to invest internally in developing and deploying our platform capabilities, including innovative genome editing, delivery and cell engineering technologies to advance new therapeutic programs.
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As of December 31, 2024 and 2023, cash equivalents consisted of interest-bearing money market accounts, U.S. Treasury bills and other government securities. Restricted Cash Equivalents The Company has restricted cash equivalents made up of money market funds held in collateral accounts that are restricted to secure letters of credit in accordance with certain of its leases.
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We will also continue to explore accessing external technologies or opportunities to enhance our leadership position in developing innovative therapeutics.
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As of December 31, 2024 and 2023, these restricted cash equivalents amounted to $ 13.6 million . The letters of credit are required to be maintained throughout the term of the leases; in some cases, the Company is able to reduce the amounts held over time.
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Our Pipeline The following table summarizes the status of our most advanced programs: In Vivo Programs Our selection criteria include identifying diseases that originate in the liver; have well-defined mutations that can be addressed by a knockout or insertion approach; have readily measurable therapeutic endpoints with observable clinical responses; and for which effective treatments are absent, limited or unduly burdensome.
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These restricted cash equivalents are long-term in nature and are included in “Investments and other assets” in the Company’s consolidated balance sheets. Marketable Securities The Company’s marketable securities are accounted for as available-for-sale and recorded at fair value with the related unrealized gains and losses included in accumulated other comprehensive (loss) income, a component of stockholders’ equity.
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Our initial in vivo indications target genetic liver diseases, including our ATTR amyloidosis, HAE and AATD development programs. Our current efforts on in vivo delivery focus on the use of LNPs for delivery of the CRISPR/Cas9 complex to the liver.
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The Company reviews its investment portfolio to identify and evaluate investments that have an indication of possible other-than-temporary impairment.
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Transthyretin (“ATTR”) Amyloidosis Program Background ATTR amyloidosis is a progressive and fatal disorder resulting from deposition of insoluble amyloid fibrils into multiple organs and tissues leading to systemic failure.
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Factors considered in determining whether a loss is other-than-temporary include the length of time and extent to which fair value has been less than the cost basis, the financial condition and near-term prospects of the investee, and the Company’s intent and ability to hold the investment for a period of time sufficient to allow for any anticipated recovery in market value.
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Blood-borne transthyretin (“TTR”) protein is produced by hepatocytes and normally circulates as a soluble homotetramer that facilitates transport of vitamin A, via retinol binding protein, as well as the thyroid hormone, thyroxine. Mutations in the TTR gene lead to the production of TTR proteins that are destabilized in their tetramer form.
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Refer to Note 3 for further information regarding the Company’s marketable securities.
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These tetramers more readily dissociate into the monomeric form, and thence to an aggregative form that results in amyloid deposits in tissues. These deposits cause damage in those tissues, resulting in a disorder known as hereditary ATTR amyloidosis (“ATTRv”). Over 120 different genetic mutations are currently known to cause ATTRv.
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Investments in Equity Securities Investments in equity securities, other than equity method investments, are recorded at fair market value if fair value is readily determinable and any gains and losses are included in “Change in fair value of investments, net,” on the consolidated statement of operations and comprehensive loss.
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Deposits of TTR amyloid in the heart, nerves and/or other tissues can lead to diverse disease manifestations, including two main hereditary forms – ATTRv with polyneuropathy (“ATTRv-PN”), and ATTRv with cardiomyopathy 8 (“ATTRv-CM”). Typical onset of disease symptoms is during adulthood and can be fatal within two to 15 years. Estimates suggest that approximately 50,000 patients suffer from ATTRv worldwide.
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In the absence of a readily determinable fair value, the Company measures the investment at cost less impairment, plus or minus observable changes, if any. These investments are included in “Investments and other assets” in the Company’s consolidated balance sheets. Refer to Note 10 for further information regarding the Company’s investments in equity securities.
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In addition to the hereditary forms described above, ATTR amyloidosis can also develop spontaneously in the absence of any TTR gene mutation. This wild-type ATTR (“ATTRwt”) is increasingly being recognized as a significant and often undiagnosed cause of heart failure in the elderly and is the subject of active investigation.
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Asset Acquisitions At the time of acquisition, the Company determines if a transaction should be accounted for as a business combination or acquisition of assets.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeAdditionally, because our in vivo technology potentially involves genome editing across multiple cell and tissue types, we are subject to many of the challenges and risks that other genome editing therapeutics and gene therapies face, including: • regulatory guidance regarding the requirements governing gene and genome editing therapy products have changed and may continue to change in the future, including, e.g., the finalized guidance document titled “Human Gene Therapy Products Incorporating Human Genome Editing” that the FDA issued in January 2024; • to date, only a limited number of products that involve in vivo gene transfer have been approved globally; • improper modulation of a gene sequence, including unintended editing events, insertion of a sequence into certain locations in a patient’s chromosome or other effects related to the biodistribution of our product candidates, could lead to cancer, other aberrantly functioning cells or other diseases, including death; • transient expression of the Cas9 protein or other genome editing components of our product candidates could lead to patients having an immunological reaction towards those cells, which could be severe or life-threatening; • corrective expression of a missing protein in patients’ cells could result in the protein being recognized as foreign, and lead to a sustained immunological reaction against the expressed protein or expressing cells, which could be severe or life-threatening; and • regulatory agencies may require extended follow-up observation periods of patients who receive treatment using genome editing products including, for example, the FDA’s recommended 15-year follow-up observation period for these patients, and we will need to adopt such observation periods for our product candidates if required by the relevant regulatory agency, which could vary by country or region.
Biggest changeAdditionally, because our in vivo technology potentially involves genome editing across multiple cell and tissue types, we are subject to many of the challenges and risks that other genome editing therapeutics and gene therapies face, including: • regulatory guidance for gene and genome editing therapy products has changed and may continue to change in the future, including, e.g., the finalized guidance document titled “Human Gene Therapy Products Incorporating Human Genome Editing” that the FDA issued in January 2024 and the draft guidance document titled “Frequently Asked Questions — Developing Potential Cellular and Gene Therapy Products” published in November 2024; • to date, only a limited number of products that involve in vivo gene transfer have been approved globally; • improper modulation of a gene sequence, including unintended editing events, insertion of a sequence into certain locations in a patient’s chromosome or other effects related to the biodistribution of our product candidates, could lead to cancer, other aberrantly functioning cells or other diseases, including death; • transient expression of the Cas9 protein or other genome editing components of our product candidates could lead to patients having an immunological reaction towards those modified cells, which could be severe or life-threatening; • corrective expression of a missing protein in patients’ cells could result in the protein being recognized as foreign, and lead to a sustained immunological reaction against the expressed protein or expressing cells, which could be severe or life-threatening; and • regulatory agencies may require extended follow-up observation periods of patients who receive treatment using genome editing products including, for example, the FDA’s recommended 15-year follow-up observation period for these patients, and we will need to adopt such observation periods for our product candidates if required by the relevant regulatory agency, which could vary by country or region. 37 Further, because our ex vivo product candidates involve editing human cells and then delivering modified cells to patients, we are subject to many of the challenges and risks that engineered cell therapies face.
For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the Securities and Exchange Commission (the “SEC”), have had to furlough critical FDA, SEC and other government employees and stop critical activities.
For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the Securities and Exchange Commission (“SEC”), have had to furlough critical FDA, SEC and other government employees and stop critical activities.
Our ability to generate revenue, and achieve and retain profitability, depends significantly on our success in many areas, including: • obtaining regulatory approvals and marketing authorizations for our lead programs; • obtaining market acceptance of our product candidates as viable treatment options; • launching and commercializing product candidates for which we obtain regulatory approvals and marketing authorizations, either directly or with a collaborator or distributor; • accurately assessing the size and addressability of potential patient populations; • addressing any competing technological and market developments; • maintaining, protecting and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; • avoiding infringement of or obtaining licenses to any valid intellectual property owned or controlled by third parties; • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter or which may be necessary for us to develop, manufacture or commercialize our product candidates; • maintaining good relationships with our collaborators and licensors; • attracting, hiring and retaining qualified personnel; • developing a sustainable and scalable manufacturing process for product candidates, including establishing and maintaining commercially viable supply relationships with third parties, such as CMOs, and potentially establishing our own manufacturing capabilities and infrastructure; • successfully completing research, preclinical and clinical development of product candidates; 59 • investing resources in developing commercial manufacturing and operational infrastructure prior to clinical evidence of safety and efficacy for a given product candidate; and • selecting commercially viable product candidates and effective delivery methods.
Our ability to generate revenue, and achieve and retain profitability, depends significantly on our success in many areas, including: • obtaining regulatory approvals and marketing authorizations for our lead programs; • obtaining market acceptance of our product candidates as viable treatment options; • launching and commercializing product candidates for which we obtain regulatory approvals and marketing authorizations, either directly or with a collaborator or distributor; • accurately assessing the size and addressability of potential patient populations; • addressing any competing technological and market developments; • maintaining, protecting and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; • avoiding infringement of or obtaining licenses to any valid intellectual property owned or controlled by third parties; • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter or which may be necessary for us to develop, manufacture or commercialize our product candidates; • maintaining good relationships with our collaborators and licensors; • attracting, hiring and retaining qualified personnel; • developing a sustainable and scalable manufacturing process for product candidates, including establishing and maintaining commercially viable supply relationships with third parties, such as CMOs, and potentially establishing our own manufacturing capabilities and infrastructure; • successfully completing research, preclinical and clinical development of product candidates; • investing resources in developing commercial manufacturing and operational infrastructure prior to clinical evidence of safety and efficacy for a given product candidate; and • selecting commercially viable product candidates and effective delivery methods.
Our stock price is likely to continue to be volatile and subject to significant price and volume fluctuations in response to market and other factors, including: • the success of our products or technologies or competing products or technologies; • results of clinical trials of our product candidates or those of our competitors; • developments or disputes concerning issued patents, patent applications or other intellectual property rights; • regulatory or legal developments in the U.S. and other countries; • the recruitment or departure of key personnel; • the level of expenses related to any of our product candidates or clinical development programs; • the results of our efforts to discover, develop, manufacture, acquire or in-license our current and additional product candidates or products; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or the financial results of companies that are perceived to be similar to us; • sales of a substantial number of shares of our common stock in the public market, or the perception in the market that the holders of a large number of shares intend to sell shares; • changes in the structure of healthcare payment systems; 83 • market conditions in the pharmaceutical and biotechnology sectors; • public perception of the safety of genome editing based therapeutics; • general economic, industry and market conditions; and • the other factors summarized and described in this Risk Factors section.
Our stock price is likely to continue to be volatile and subject to significant price and volume fluctuations in response to market and other factors, including: • the success of our products or technologies or competing products or technologies; • results of clinical trials of our product candidates or those of our competitors; • developments or disputes concerning issued patents, patent applications or other intellectual property rights; • regulatory or legal developments in the U.S. and other countries; • the recruitment or departure of key personnel; • the level of expenses related to any of our product candidates or clinical development programs; • the results of our efforts to discover, develop, manufacture, acquire or in-license our current and additional product candidates or products; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or the financial results of companies that are perceived to be similar to us; • sales of a substantial number of shares of our common stock in the public market, or the perception in the market that the holders of a large number of shares intend to sell shares; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • public perception of the safety of genome editing based therapeutics; • general economic, industry and market conditions; and • the other factors summarized and described in this Risk Factors section.
We also may experience numerous unforeseen events during, or as a result of, any current or future clinical trials that we conduct, which could delay or prevent our ability to receive marketing approval or commercialize our product candidates, including: • challenges in obtaining regulatory authorization or approval to conduct clinical trials in the U.S. from the FDA through an investigational new drug (“IND”) application or from other regulatory agencies outside the U.S., such as the United Kingdom (“U.K.”) Medicines and Healthcare products Regulatory Agency (“MHRA”) or the European Medicines Agency (“EMA”), through corresponding applications, such as a clinical trial application, a Clinical Trial Notification or a Clinical Trial Exemption, because these agencies have very limited or no experience with the clinical development of CRISPR/Cas9-based therapeutics, particularly in vivo therapeutics, which may require additional significant testing or data compared to more traditional therapies or otherwise delay the development of our product candidates; • successfully developing processes for the safe administration of these product candidates, including long-term follow-up for patients who receive treatment with any of our product candidates; • regulators, institutional review boards (“IRBs”) or ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial; • inability to reach, or delays in reaching, agreement on acceptable terms with trial sites and contract research organizations (“CROs”); • clinical trials of any product candidates may fail to show safety or efficacy, or could produce negative or inconclusive results, which could result in having to conduct additional preclinical studies or clinical trials or terminating the product development programs; • we may not be able to initiate or complete clinical trials of a product candidate if the required number of subjects is larger than we anticipated, the number of subjects willing to enroll is smaller than required, the 43 pace of enrollment is slower than anticipated, or subjects drop out or fail to return for post-treatment follow-up at a higher rate than we anticipated; • we may need to educate medical personnel, including clinical investigators, and patients regarding the potential benefits and side effect profile of each of our product candidates; • regulatory agencies may require us to amend our INDs or equivalent regulatory filings, modify the design of our clinical trials or perform more extensive or lengthier preclinical or clinical testing compared to existing therapeutic modalities, any of which may delay the initiation or progression of any of our clinical trials; • animal models may not exist, or available animal models may be inadequate, for some of the human diseases we choose to pursue in our programs, or the preclinical studies we perform as part of our programs; • our third party contractors may fail to comply with regulatory requirements or meet their performance obligations to us in a timely manner, or at all, or may deviate from the clinical trial protocol or drop out of the trial, which may require that we add new clinical trial sites or investigators; • we may elect to, or regulators, IRBs or ethics committees may require that we or our investigators, suspend or terminate clinical research or trials for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; • the cost of preclinical studies and clinical trials of any product candidates may be greater than we anticipate; • the supply or quality of our product candidates or other materials necessary to conduct preclinical studies and clinical trials of our product candidates may be insufficient or inadequate, or not available in a reasonable timeframe, and any transfer of manufacturing activities may require unforeseen manufacturing or formulation changes; • we may face challenges in sourcing preclinical, clinical and, if approved, commercial supplies for the materials used to manufacture and process our product candidates, which may include importing or exporting materials between different jurisdictions; • our product candidates may have undesirable side effects or other unexpected characteristics, such as effects or characteristics resulting from their biodistribution or mechanism of action, causing us or our investigators, regulators, IRBs or ethics committees to suspend or terminate the trials, or reports may arise from preclinical or clinical testing of other gene therapies or genome editing-based therapies that raise safety or efficacy concerns about our product candidates; • the FDA or other regulatory authorities may require us to submit additional data, such as long-term toxicology studies, or impose other requirements, including submitting preclinical data earlier in clinical development compared to existing therapeutic modalities or requiring amendments to our regulatory filings, before permitting us to initiate or rely on a clinical trial; • we may face challenges in establishing sales and marketing capabilities in anticipation of, and after obtaining, any regulatory approval to gain market authorization; • the FDA or other regulatory authorities may revise the requirements for authorizing our clinical trials or approving our product candidates, or their interpretation of the authorization or approval requirements may not be what we anticipate or require us to adopt a Risk Evaluation and Mitigation Strategy (“REMS”) or similar requirements as a condition of approval; and • we may not ultimately obtain regulatory approval for a BLA, or corresponding applications outside the U.S., such as a marketing authorization application in the U.K. and other similar regulatory authorities, such as the EMA, which may have very limited or no experience with the clinical development of CRISPR/Cas9-based therapeutics, particularly in vivo therapeutics.
We also may experience numerous unforeseen events during, or as a result of, any current or future clinical trials that we conduct, which could delay or prevent our ability to receive marketing approval or commercialize our product candidates, including: • challenges in obtaining regulatory authorization or approval to conduct clinical trials in the U.S. from the FDA through an investigational new drug (“IND”) application or from other regulatory agencies outside the U.S., such as the United Kingdom (“U.K.”) Medicines and Healthcare products Regulatory Agency (“MHRA”) or the European Medicines Agency (“EMA”), through corresponding applications, such as a clinical trial application, a clinical trial notification or a clinical trial exemption, because these agencies have very limited or no experience with the clinical development of CRISPR/Cas9-based therapeutics, particularly in vivo therapeutics, which may require additional significant testing or data compared to more traditional therapies or otherwise delay the development of our product candidates; • successfully developing processes for the safe administration of these product candidates, including long-term follow-up for patients who receive treatment with any of our product candidates; • regulators, institutional review boards (“IRBs”) or ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial; • inability to reach, or delays in reaching, agreement on acceptable terms with trial sites and contract research organizations (“CROs”); • clinical trials of any product candidates may fail to show safety or efficacy, or could produce negative or inconclusive results, which could result in having to conduct additional preclinical studies or clinical trials or terminating the product development programs; • we may not be able to initiate or complete clinical trials of a product candidate if the required number of subjects is larger than we anticipated, the number of subjects willing to enroll is smaller than required, the pace of enrollment is slower than anticipated, or subjects drop out or fail to return for post-treatment follow-up at a higher rate than we anticipated; • we may need to educate medical personnel, including clinical investigators, and patients regarding the potential benefits and side effect profile of each of our product candidates; • regulatory agencies may require us to amend our INDs or equivalent regulatory filings, modify the design of our clinical trials or perform more extensive or lengthier preclinical or clinical testing compared to existing therapeutic modalities, any of which may delay the initiation or progression of any of our clinical trials; • animal models may not exist, or available animal models may be inadequate, for some of the human diseases we choose to pursue in our programs, or the preclinical studies we perform as part of our programs; • our third party contractors, clinical trial sites or investigators may fail to comply with regulatory requirements or meet their performance obligations to us in a timely manner, or at all, or may deviate from the clinical trial protocol or drop out of the trial, which may require that we add new clinical trial sites or investigators; • we may elect to, or regulators, IRBs or ethics committees may require that we or our investigators, suspend or terminate clinical research or trials for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; • the cost of preclinical studies and clinical trials of any product candidates may be greater than we anticipate; • the supply or quality of our product candidates or other materials necessary to conduct preclinical studies and clinical trials of our product candidates may be insufficient or inadequate, or not available in a reasonable timeframe, and any transfer of manufacturing activities may require unforeseen manufacturing or formulation changes; • we may face challenges in sourcing preclinical, clinical and, if approved, commercial supplies for the materials used to manufacture and process our product candidates, which may include importing or exporting materials between different jurisdictions; 36 • our product candidates may have undesirable side effects or other unexpected characteristics, such as effects or characteristics resulting from their biodistribution or mechanism of action, causing us or our investigators, regulators, IRBs or ethics committees to suspend or terminate the trials, or reports may arise from preclinical or clinical testing of other gene therapies or genome editing-based therapies that raise safety or efficacy concerns about our product candidates; • the FDA or other regulatory authorities may require us to submit additional data, such as long-term toxicology studies, or impose other requirements, including submitting preclinical data earlier in clinical development compared to existing therapeutic modalities or requiring amendments to our regulatory filings, before permitting us to initiate or rely on a clinical trial; • we may face challenges in establishing sales and marketing capabilities in anticipation of, and after obtaining, any regulatory approval to gain market authorization; • the FDA or other regulatory authorities may revise the requirements for authorizing our clinical trials or approving our product candidates, or their interpretation of the authorization or approval requirements may not be what we anticipate or require us to adopt Risk Evaluation and Mitigation Strategy (“REMS”) as a condition of approval; and • we may not ultimately obtain regulatory approval for a BLA, or corresponding applications outside the U.S., such as a marketing authorization application in the U.K. and other similar regulatory authorities, which may have very limited or no experience with the clinical development of CRISPR/Cas9-based therapeutics, particularly in vivo therapeutics.
Our existing and future therapeutic collaborations may have a number of risks, including that collaborators: • have significant discretion in determining the efforts and resources that they will apply; 70 • may not perform their obligations as expected; • may dispute the amounts of payments owed; • may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs or license arrangements based on clinical trial results, changes in their strategic focus or available funding, or external factors, such as a strategic transaction that may divert resources or create competing priorities; • may delay, insufficiently fund, stop, initiate new or repeat clinical trials, reformulate a product candidate for clinical testing, or abandon a product candidate; • could develop independently, or with third parties, products that compete directly or indirectly with our products and product candidates; • may view product candidates discovered in our collaborations as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the development or commercialization of our product candidates; • may dispute ownership or rights in jointly developed technologies or intellectual property; • may fail to comply with applicable legal and regulatory requirements regarding the development, manufacture, sale, distribution or marketing of a product candidate or product; • with sales, marketing, manufacturing and distribution rights to our product candidates may not commit sufficient resources to the product’s sale, marketing, manufacturing and distribution; • may disagree with us about material issues, including proprietary rights, contract interpretation, payment obligations or the preferred course of discovery, development, sales or marketing, which might cause delays or terminations of the research, development or commercialization of product candidates, lead to additional and burdensome responsibilities for us with respect to product candidates, or result in litigation or arbitration, any of which would be time-consuming and expensive; • may not properly maintain or defend their or our relevant intellectual property rights or may use our proprietary information or sublicensed intellectual property rights in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation and liability; • may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; • could become involved in a business combination or cessation that could cause them to deemphasize or terminate the development or commercialization of any product candidate licensed to it by us; and • may terminate our collaborations, which could require us to raise additional capital to develop or commercialize the applicable product candidates, or lose access to the collaborator’s intellectual property.
Our existing and future therapeutic collaborations may have a number of risks, including that collaborators: • have significant discretion in determining the efforts and resources that they will apply; • may not perform their obligations as expected; • may dispute the amounts of payments owed; • may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs or license arrangements based on clinical trial results, changes in their strategic focus or available funding, or external factors, such as a strategic transaction that may divert resources or create competing priorities; • may delay, insufficiently fund, stop, initiate new or repeat clinical trials, reformulate a product candidate for clinical testing, or abandon a product candidate; • could develop independently, or with third parties, products that compete directly or indirectly with our products and product candidates; • may view product candidates discovered in our collaborations as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the development or commercialization of our product candidates; • may dispute ownership or rights in jointly developed technologies or intellectual property; • may fail to comply with applicable legal and regulatory requirements regarding the development, manufacture, sale, distribution or marketing of a product candidate or product; • with sales, marketing, manufacturing and distribution rights to our product candidates may not commit sufficient resources to the product’s sale, marketing, manufacturing and distribution; • may disagree with us about material issues, including proprietary rights, contract interpretation, payment obligations or the preferred course of discovery, development, sales or marketing, which might cause delays or terminations of the research, development or commercialization of product candidates, lead to additional and burdensome responsibilities for us with respect to product candidates, or result in litigation or arbitration, any of which would be time-consuming and expensive; • may not properly maintain or defend their or our relevant intellectual property rights or may use our proprietary information or sublicensed intellectual property rights in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation and liability; • may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; 60 • could become involved in a business combination or cessation that could cause them to deemphasize or terminate the development or commercialization of any product candidate licensed to it by us; and • may terminate our collaborations, which could require us to raise additional capital to develop or commercialize the applicable product candidates, or lose access to the collaborator’s intellectual property.
Among other things, the certificate of incorporation and by-laws: • permit the board of directors to issue up to 5,000,000 shares of preferred stock, with any rights, preferences and privileges as they may designate; • provide that the authorized number of directors may be changed only by resolution of the board of directors; • provide that all vacancies, including newly created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum; • divide the board of directors into three classes; • provide that a director may only be removed from the board of directors by the stockholders for cause; 86 • require that any action to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders, and may not be taken by written consent; • provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide notice in writing in a timely manner, and meet specific requirements as to the form and content of a stockholder’s notice; • prevent cumulative voting rights (therefore allowing the holders of a plurality of the shares of common stock entitled to vote in any election of directors to elect all of the directors standing for election, if they should so choose); • require that, to the fullest extent permitted by law, a stockholder reimburse us for all fees, costs and expenses incurred by us in connection with a proceeding initiated by such stockholder in which such stockholder does not obtain a judgment on the merits that substantially achieves the full remedy sought; • provide that special meetings of our stockholders may be called only by the chairman of the board, our chief executive officer (or president, in the absence of a chief executive officer) or by the board of directors; and • provide that stockholders will be permitted to amend the bylaws only upon receiving at least two-thirds of the total votes entitled to be cast by holders of all outstanding shares then entitled to vote generally in the election of directors, voting together as a single class.
Among other things, the certificate of incorporation and by-laws: • permit the board of directors to issue up to 5,000,000 shares of preferred stock, with any rights, preferences and privileges as they may designate; • provide that the authorized number of directors may be changed only by resolution of the board of directors; • provide that all vacancies, including newly created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum; • divide the board of directors into three classes; • provide that a director may only be removed from the board of directors by the stockholders for cause; • require that any action to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders, and may not be taken by written consent; • provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide notice in writing in a timely manner, and meet specific requirements as to the form and content of a stockholder’s notice; • prevent cumulative voting rights (therefore allowing the holders of a plurality of the shares of common stock entitled to vote in any election of directors to elect all of the directors standing for election, if they should so choose); 73 • require that, to the fullest extent permitted by law, a stockholder reimburse us for all fees, costs and expenses incurred by us in connection with a proceeding initiated by such stockholder in which such stockholder does not obtain a judgment on the merits that substantially achieves the full remedy sought; • provide that special meetings of our stockholders may be called only by the chairman of the board, our chief executive officer (or president, in the absence of a chief executive officer) or by the board of directors; and • provide that stockholders will be permitted to amend the bylaws only upon receiving at least two-thirds of the total votes entitled to be cast by holders of all outstanding shares then entitled to vote generally in the election of directors, voting together as a single class.
However, we cannot predict: • if and when any patents will issue; • the scope, degree and range of protection any issued patents will afford us against competitors, including whether third parties will find ways to invalidate or otherwise circumvent our patents; • whether others will apply for or obtain patents claiming aspects similar to those covered by our patents and patent applications; • whether certain governments will appropriate our intellectual property rights and allow competitors to use them; or • whether we will need to initiate litigation or administrative proceedings to assert or defend our patent rights, which may be costly whether we win or lose.
However, we cannot predict: • if and when any patents will issue; • the scope, degree and range of protection any issued patents will afford us against competitors, including whether third parties will find ways to invalidate or otherwise circumvent our patents; 45 • whether others will apply for or obtain patents claiming aspects similar to those covered by our patents and patent applications; • whether certain governments will appropriate our intellectual property rights and allow competitors to use them; or • whether we will need to initiate litigation or administrative proceedings to assert or defend our patent rights, which may be costly whether we win or lose.
Such authorities may impose or recommend such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities, resulting in the imposition of a clinical hold, manufacturing or quality control issues, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product or treatment, failure to establish or achieve clinically meaningful trial endpoints, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
Such authorities may impose or recommend such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our study protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities, resulting in the imposition of a clinical hold, manufacturing or quality control issues, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product or treatment, failure to establish or achieve clinically meaningful trial endpoints, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
If the results of our clinical studies or those of any other third parties, including with respect to genome editing technology or engineered cell therapies, are inconclusive or fail to show efficacy or if such clinical trials give rise to safety concerns or adverse events, we may: • be prevented from, or delayed in, obtaining marketing approval for our product candidates; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • be subject to the addition of labeling statements, such as warnings or contraindications, or other types of regulatory restrictions or scrutiny; • be subject to changes in the way the product is administered; • be required to perform additional clinical studies to support approval or be subject to additional post-marketing testing requirements; • have regulatory authorities modify or withdraw their legal requirements or written guidance, if any, regarding the applicable regulatory approval pathway or any approval of the product in question, or impose restrictions on its distribution in the form of a modified REMS or similar strategy; • be sued; or • experience damage to our reputation. 47 Additionally, our product candidates could potentially cause other adverse events that have not yet been predicted and the potentially permanent nature of genome editing effects, including CRISPR/Cas9’s effects, on genes or novel cell therapies in the organs of the human body may make these adverse events irreversible.
If the results of our clinical studies or those of any other third parties, including with respect to genome editing technology or engineered cell therapies, are inconclusive or fail to show efficacy or if such clinical trials give rise to safety concerns or adverse events, we may: • be prevented from, or delayed in, obtaining marketing approval for our product candidates; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • be subject to the addition of labeling statements, such as warnings or contraindications, or other types of regulatory restrictions or scrutiny; • be subject to changes in the way the product is administered; • be required to perform additional clinical studies to support approval or be subject to additional post-marketing testing requirements; • have regulatory authorities modify or withdraw their legal requirements or written guidance, if any, regarding the applicable regulatory approval pathway or any approval of the product in question, or impose restrictions on its distribution in the form of a modified REMS or similar strategy; • be sued; or • experience damage to our reputation. 39 Additionally, our product candidates could potentially cause other adverse events that have not yet been predicted and the potentially permanent nature of genome editing effects, including CRISPR/Cas9’s effects, on genes or novel cell therapies in the organs of the human body may make these adverse events irreversible.
Pursuant to the terms of the license agreements with our licensors, the licensors may have the right to control enforcement of our licensed patents or defense of any claims asserting the invalidity of these patents and, even if we are permitted to pursue such 52 enforcement or defense, we cannot ensure the cooperation of our licensors or, in some cases, other necessary parties, such as the co-owners of the intellectual property from which we have not yet obtained a license.
Pursuant to the terms of the license agreements with our licensors, the licensors may have the right to control enforcement of our licensed patents or defense of any claims asserting the invalidity of these patents and, even if we are permitted to pursue such enforcement or defense, we cannot ensure the cooperation of our licensors or, in some cases, other necessary parties, such as the co-owners of the intellectual property from which we have not yet obtained a license.
New risk factors can emerge from time to time, and we cannot predict the impact that any factor or combination of factors may have on our business, prospects, financial condition and results of operations. 41 Risks Related to Our Business Risks Related to Preclinical and Clinical Development CRISPR/Cas9 genome editing technology has only recently been clinically validated for human therapeutic use.
New risk factors can emerge from time to time, and we cannot predict the impact that any factor or combination of factors may have on our business, prospects, financial condition and results of operations. Risks Related to Our Business Risks Related to Preclinical and Clinical Development CRISPR/Cas9 genome editing technology has only recently been clinically validated for human therapeutic use.
Successful development of products by us will require solving a number of issues, including developing or obtaining technologies to safely deliver a therapeutic agent into target cells within the human body or engineer human cells while outside of the body such that the modified cells can have a therapeutic effect when delivered to the patient, optimizing the efficacy and specificity of such products, and ensuring and demonstrating the therapeutic selectivity, efficacy, potency, purity and safety of such products.
Successful development of products by us will require solving a number of issues, including developing or obtaining technologies to safely deliver a therapeutic agent into target cells within the human body or engineer human cells while outside of the body such that the modified cells can have a therapeutic effect when delivered to the patient, optimizing the efficacy and specificity of such products, and demonstrating the therapeutic selectivity, efficacy, potency, purity and safety of such products.
In addition, the use of the technology by third parties in areas that are not being pursued by us, such as for targeting and editing of embryonic cells, could adversely impact public and governmental perceptions regarding the ethics and risks of the CRISPR/Cas9 technology and lead to social or legal changes that could limit our ability to apply the technology to develop human therapies addressing disease.
In addition, the use of genome editing technology by third parties in areas that are not being pursued by us, such as for targeting and editing of embryonic cells, could adversely impact public and governmental perceptions regarding the ethics and risks of CRISPR/Cas9 technology and lead to social or legal changes that could limit our ability to apply the technology to develop human therapies addressing disease.
Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.
Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our 46 owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.
The legal systems of certain countries, such as China, Brazil, Russia, India and South Africa, do not favor the enforcement of patents, trade secrets and other intellectual property, particularly those relating to biopharmaceutical products, which could make it difficult in those jurisdictions for us to stop the infringement or 56 misappropriation of our patents or other intellectual property rights, or the marketing of competing products in violation of our proprietary rights.
The legal systems of certain countries, such as China, Brazil, Russia, India and South Africa, do not favor the enforcement of patents, trade secrets and other intellectual property, particularly those relating to biopharmaceutical products, which could make it difficult in those jurisdictions for us to stop the infringement or misappropriation of our patents or other intellectual property rights, or the marketing of competing products in violation of our proprietary rights.
This program is intended to facilitate efficient development and expedite review of RMATs. A BLA for a product candidate with RMAT designation may be eligible for priority review or accelerated approval through (1) surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit or (2) reliance upon data obtained 65 from a meaningful number of sites.
This program is intended to facilitate efficient development and expedite review of RMATs. A BLA for a product candidate with RMAT designation may be eligible for priority review or accelerated approval through (1) surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit or (2) reliance upon data obtained from a meaningful number of sites.
It is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations.
It is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to 57 detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations.
Our future capital requirements will depend on and could increase significantly as a result of many factors, including the scope, progress, results and costs of drug discovery, preclinical development, laboratory testing and clinical trials for our current or future product candidates, including additional expenses attributable to adjusting our development plans (including any supply related matters).
Our future capital requirements will depend on and could increase significantly as a result of many factors, including the scope, progress, results and costs of drug discovery, preclinical development, laboratory 51 testing and clinical trials for our current or future product candidates, including additional expenses attributable to adjusting our development plans (including any supply related matters).
Pending our use to fund operations, we may invest our cash, cash equivalents and marketable securities in a manner that does not produce income or that loses value. 84 A portion of our cash may be held by financial institutions that may have been, or could in the future become, exposed to liquidity issues, bank failures or other systemic financial risks.
Pending our use to fund operations, we may invest our cash, cash equivalents and marketable securities in a manner that does not produce income or that loses value. A portion of our cash may be held by financial institutions that may have been, or could in the future become, exposed to liquidity issues, bank failures or other systemic financial risks.
In addition, any material alteration, in an adverse manner, of any material collaboration agreement, or dispute or litigation proceedings we may have related to a material collaboration in the future could delay development programs, create uncertainty as to ownership of or access to intellectual property rights, distract management from other business activities and generate substantial expense.
In addition, any material alteration, in an adverse manner, of any 59 material collaboration agreement, or dispute or litigation proceedings we may have related to a material collaboration in the future could delay development programs, create uncertainty as to ownership of or access to intellectual property rights, distract management from other business activities and generate substantial expense.
In addition, the collection and use of personal information, including Protected Health Information (“PHI”), is regulated by federal, state and foreign privacy, data security and data protection laws. Failure to comply with these laws could impair our ability to properly sell our product candidates in particular jurisdictions and subject us to liability from private and governmental entities.
In addition, the collection and use of personal information, including Protected Health Information, is regulated by federal, state and foreign privacy, data security and data protection laws. Failure to comply with these laws could impair our ability to properly sell our product candidates in particular jurisdictions and subject us to liability from private and governmental entities.
If we are not able to generate revenue from the sale of any approved products, we may never become profitable. Our operating history may make difficult the evaluation of our business’s success to date and assessment of our future viability. We are a clinical-stage company. We were founded and commenced operations in mid-2014.
If we are not able to generate revenue from the sale of any approved products, we may never become profitable. 50 Our operating history may make difficult the evaluation of our business’s success to date and assessment of our future viability. We are a clinical-stage company. We were founded and commenced operations in mid-2014.
We cannot be sure that our CRISPR/Cas9 efforts and technologies will yield satisfactory products that are safe and effective, sufficiently pure or potent, manufacturable, scalable or profitable in our selected indications or any other indication we pursue. We cannot guarantee that progress or success in developing any particular CRISPR/Cas9-based therapeutic product will translate to other CRISPR/Cas9-based products.
We cannot be sure that our CRISPR/Cas9 efforts and technologies will yield satisfactory products that are safe and effective, sufficiently pure or potent, manufacturable, scalable or profitable in our selected 34 indications or any other indication we pursue. We cannot guarantee that progress or success in developing any particular CRISPR/Cas9-based therapeutic product will translate to other CRISPR/Cas9-based products.
In order to maintain our intellectual property rights under these agreements, we will need to meet certain specified 53 milestones, subject to certain cure provisions, in the development of our product candidates. Further, our counterparties, including our licensors (or their licensors) or licensees, may dispute the terms, including amounts, that we are required to pay under the respective agreements.
In order to maintain our intellectual property rights under these agreements, we will need to meet certain specified milestones, subject to certain cure provisions, in the development of our product candidates. Further, our counterparties, including our licensors (or their licensors) or licensees, may dispute the terms, including amounts, that we are required to pay under the respective agreements.
In the U.S., numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state health information privacy laws, and federal and 68 state consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the operations of our collaborators.
In the U.S., numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the operations of our collaborators.
Specific to our NTLA-2002 program, we are aware of other companies that are currently commercializing or developing products used to treat HAE, including ADARx Therapeutics, Inc., Astria Therapeutics Inc., BioCryst Pharmaceuticals Inc., BioMarin Pharmaceuticals Inc., CSL Limited, Ionis Pharmaceuticals, Inc., KalVista Pharmaceuticals, Inc., Pharming Group N.V., Pharvaris N.V. and Takeda Pharmaceutical Company Limited.
Specific to our NTLA-2002 program, we are aware of other companies that are currently commercializing or developing products used to treat HAE, including ADARx Therapeutics, Inc., Astria Therapeutics Inc., BioCryst Pharmaceuticals Inc., CSL Limited, Ionis Pharmaceuticals, Inc., KalVista Pharmaceuticals, Inc., Pharming Group N.V., Pharvaris N.V. and Takeda Pharmaceutical Company Limited.
We could also encounter delays if a clinical trial is suspended or terminated by us, the IRBs of the institutions in which such trials are being conducted, the relevant ethics committee or the FDA or other relevant regulatory authorities, or 44 if the Data Monitoring Committee (“DMC”) for such trial recommends such suspension or termination.
We could also encounter delays if a clinical trial is suspended or terminated by us, the IRBs of the institutions in which such trials are being conducted, the relevant ethics committee or the FDA or other relevant regulatory authorities, or if the Data Monitoring Committee (“DMC”) for such trial recommends such suspension or termination.
For the reasons described above, among others, regulatory bodies, particularly the FDA, have requested, and may request in the future, additional 45 preclinical studies for genome editing products, such as additional studies related to toxicology, biodistribution or reproductive health, and/or preclinical studies earlier in clinical development compared to other therapeutic modalities.
For the reasons described above, among others, regulatory bodies, particularly the FDA, have requested, and may request in the future, additional preclinical studies for genome editing products, such as additional studies related to toxicology, biodistribution or reproductive health, and/or preclinical studies earlier in clinical development compared to other therapeutic modalities.
Patent and Trademark Office (“USPTO”) declared an interference between the UC/Vienna/Charpentier eukaryotic patent family and the Broad Institute patent 50 family to determine which research group first invented the use of the CRISPR/Cas9 technology in eukaryotic cells and, therefore, is entitled to the U.S. patents covering that invention.
Patent and Trademark Office (“USPTO”) declared an interference between the UC/Vienna/Charpentier eukaryotic patent family and the Broad Institute patent family to determine which research group first invented the use of the CRISPR/Cas9 technology in eukaryotic cells and, therefore, is entitled to the U.S. patents covering that invention.
Physicians may not be willing to undergo training to adopt these novel and potentially personalized therapies, may decide the particular therapy is too complex or potentially risky to adopt without appropriate training, and may choose not to administer the therapy. Further, due to health conditions, genetic profile or other reasons, certain patients may not be candidates for the therapies.
Physicians may not be willing to undergo training to adopt these novel therapies, may decide the particular therapy is too complex or potentially risky to adopt without appropriate training, and may choose not to administer the therapy. Further, due to health conditions, genetic profile or other reasons, certain patients may not be candidates for the therapies.
Further, the net losses we incur may fluctuate significantly from quarter to quarter and year to year, such that a period-to-period comparison of our results of operations may not be a good indication of our future performance. 60 Risks Related to Future Financial Condition We may need to raise substantial additional funding to fund our operations.
Further, the net losses we incur may fluctuate significantly from quarter to quarter and year to year, such that a period-to-period comparison of our results of operations may not be a good indication of our future performance. Risks Related to Future Financial Condition We may need to raise substantial additional funding to fund our operations.
Any termination of these licenses, loss by our licensors of the rights they receive from others, diminution of our rights or those of our licensors, or a finding that such intellectual property lacks legal effect, could result in the 51 loss of significant rights and could harm our ability to commercialize any product candidates.
Any termination of these licenses, loss by our licensors of the rights they receive from others, diminution of our rights or those of our licensors, or a finding that such intellectual property lacks legal effect, could result in the loss of significant rights and could harm our ability to commercialize any product candidates.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, but a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, but a failure or delay in obtaining regulatory approval in 55 one jurisdiction may have a negative effect on the regulatory approval process in others.
Numerous U.S. and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we are developing our product candidates and in areas potentially related to components and methods we use or may use in our research and development efforts.
Numerous U.S. and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we are developing our product candidates and in areas potentially related to components and methods we use or may use in our research, development, and commercialization efforts.
Further, patients may choose to travel to countries in which we do not have intellectual property rights or which do not enforce these rights to obtain the products or treatment from competitors in such countries. Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
Further, patients may choose to travel to countries in which we do not have intellectual property rights or which do not enforce these rights to obtain the products or treatment from competitors in such countries. 47 Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
Furthermore, the laws of some foreign countries do not protect proprietary rights to the same extent or in the same manner as the laws of the U.S. As a result, we may encounter significant 58 problems in protecting and defending our intellectual property both in the U.S. and abroad.
Furthermore, the laws of some foreign countries do not protect proprietary rights to the same extent or in the same manner as the laws of the U.S. As a result, we may encounter significant problems in protecting and defending our intellectual property both in the U.S. and abroad.
In addition, if the FDA or a comparable foreign regulatory authority approves our product candidates, we will have to comply with their respective legal or regulatory requirements including submissions of safety and other post-marketing information and reports and registration.
In addition, if the FDA or a comparable foreign regulatory authority approves our product 56 candidates, we will have to comply with their respective legal or regulatory requirements including submissions of safety and other post-marketing information and reports and registration.
Though we carefully manage our relationships with these parties, there can be no assurance that we will not encounter similar challenges or delays in 74 the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.
Though we carefully manage our relationships with these parties, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.
Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002 (“Section 404”), we are required to furnish a report by our management on our internal control over financial reporting, including an attestation report on internal control over financial reporting issued by our independent registered public accounting firm.
Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002 (“Section 404”), we are required to furnish a report by our management on our internal control over financial reporting, including an attestation report on internal control over financial 72 reporting issued by our independent registered public accounting firm.
Orphan drug designation must be requested before submitting a BLA. In the U.S., orphan drug designation entitles a party to financial incentives such as opportunities 64 for grant funding towards clinical trial costs, tax advantages and user-fee waivers.
Orphan drug designation must be requested before submitting a BLA. In the U.S., orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.
If we obtain FDA approval of any of our product candidates and begin commercializing those products in the U.S., our potential exposure under such laws will increase significantly, and our costs associated 67 with compliance with such laws are also likely to increase.
If we obtain FDA approval of any of our product candidates and begin commercializing those products in the U.S., our potential exposure under such laws will increase significantly, and our costs associated with compliance with such laws are also likely to increase.
These different laws governing the privacy and security of health and other personal information often differ from each other in significant ways and may not have the same effective requirements, thus complicating efforts to comply with their respective provisions.
These different laws 68 governing the privacy and security of health and other personal information often differ from each other in significant ways and may not have the same effective requirements, thus complicating efforts to comply with their respective provisions.
We cannot guarantee that any of these components of our technology, processes, future product candidates or the use of such product candidates do not infringe third party patents. It is also possible that we have failed to identify relevant third party patents or applications.
We cannot guarantee that any of these components of our technology, processes, or future product candidates, or the commercialization or use of such product candidates, do not infringe third party patents. It is also possible that we have failed to identify relevant third party patents or applications.
And, on June 21, 2021, the PTAB declared another interference between the same 14 allowable patent applications in the UC/Vienna/Charpentier patent family and one patent application owned by Sigma-Aldrich Co. LLC (a subsidiary of Merck KGaA).
And, on June 21, 2021, the PTAB declared another interference between the same 14 allowable patent applications in the UC/Vienna/Charpentier eukaryotic patent family and one patent application owned by Sigma-Aldrich Co. LLC (a subsidiary of Merck KGaA).
For this reason, we will employ multiple steps to control the manufacturing process to ensure that the process results in product candidates that meet their specifications, but complications at any one step could adversely impact our manufacturing of products.
For this reason, we will employ multiple steps to control the manufacturing process to ensure that the process results in product candidates that meet their specifications, but complications 52 at any one step could adversely impact our manufacturing of products.
We may also need to rely on multiple third parties, such as partners and service providers, to meet these legal requirements, which could result in additional liability for us if they do not comply.
We may also need to rely on multiple third parties, 69 such as partners and service providers, to meet these legal requirements, which could result in additional liability for us if they do not comply.
Our trade secrets and other confidential information of ours may also be exposed through cybersecurity attacks, ransomware attacks, and other hacking attempts directed at our information technology systems and those of our employees, consultants, outside scientific advisors, contractors, vendors and collaborators.
Our trade secrets and other confidential information of ours may also be exposed through cybersecurity attacks, ransomware attacks, and other hacking attempts directed at our information technology systems and those 49 of our employees, consultants, outside scientific advisors, contractors, vendors and collaborators.
If we or our CMOs cannot successfully manufacture material that conforms to our specifications and the strict relevant regulatory requirements, we and our CMOs will not be able to secure or maintain regulatory approval for our respective manufacturing facilities.
If we or our CMOs cannot successfully manufacture material that conforms to 61 our specifications and the strict relevant regulatory requirements, we and our CMOs will not be able to secure or maintain regulatory approval for our respective manufacturing facilities.
Certain of our service providers have been subject to such attacks in the past, and while no such attacks have resulted in a material impact to our business, our company or our service providers may be materially impacted by such attacks in the future.
We and certain of our service providers have been subject to such attacks in the past, and while no such attacks have resulted in a material impact to our business, our company or our service providers may be materially impacted by such attacks in the future.
Any inactive trading market for our common stock may also impair our ability to raise capital to continue to fund our operations by selling shares and may impair our ability to acquire other companies or technologies by using our shares as consideration.
Any inactive trading market for our common stock may also impair our ability to 70 raise capital to continue to fund our operations by selling shares and may impair our ability to acquire other companies or technologies by using our shares as consideration.
If a defendant were to prevail on a legal assertion of invalidity, unpatentability and/or unenforceability, we would lose at least part, and perhaps all, of the 57 patent protection on our product candidates.
If a defendant were to prevail on a legal assertion of invalidity, unpatentability and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates.
Public perception may be influenced by claims that gene therapy or genome editing, including the use of CRISPR/Cas9, is unsafe or unethical, or carries an undue risk of side 46 effects, such as improper modification of a gene sequence in a patient’s chromosome that could lead to cancer, and gene therapy or genome editing may not gain the acceptance of the public or the medical community.
Public perception may be influenced by claims that gene therapy or genome editing, including the use of CRISPR/Cas9, is unsafe or unethical, or carries an undue risk of side effects, such as improper modification of a gene sequence in a patient’s chromosome that could lead to disease such as cancer, and gene therapy or genome editing may not gain the acceptance of the public or the medical community.
In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent.
In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found 41 to have willfully infringed a patent.
Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid in the U.S., and commercial payors are critical to new product acceptance. Government authorities and other third party payors, such as private health insurers and health maintenance organizations, decide which drugs and treatments they will cover and the amount of reimbursement.
Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid in the U.S., and commercial payors are critical to new product uptake. Government authorities and other third party payors, such as private health insurers and health maintenance organizations, decide which drugs and treatments they will cover and the amount of reimbursement.
The interference involved 14 allowable patent applications from the UC/Vienna/Charpentier eukaryotic patent family and 13 patents and one patent application from the Broad Institute patent family.
The interference involved 14 allowable patent applications from the UC/Vienna/Charpentier eukaryotic patent family 42 and 13 patents and one patent application from the Broad Institute patent family.
In evaluating us and our business, careful consideration should be given to the following risk factors, in addition to the other information set forth in this Annual Report on Form 10-K for the year ended December 31, 2023 and in other documents that we file with the SEC.
In evaluating us and our business, careful consideration should be given to the following risk factors, in addition to the other information set forth in this Annual Report on Form 10-K for the year ended December 31, 2024 and in other documents that we file with the SEC.
Risks Related to Intellectual Property Risks Related to Third Party and Licensed Intellectual Property Third party claims of intellectual property infringement against us, our licensors or our collaborators may prevent or delay our product discovery and development efforts. Our commercial success depends in part on our avoiding infringement of the valid patents and proprietary rights of third parties.
Risks Related to Intellectual Property Risks Related to Third Party and Licensed Intellectual Property Third party claims of intellectual property infringement against us, our licensors or our collaborators may prevent or delay our product discovery, research, development, and/or commercialization efforts. Our commercial success depends in part on our avoiding infringement of the valid patents and proprietary rights of third parties.
For more information on these laws and regulations see the section titled “ Business – Government Regulation and Product Approval – Other Healthcare and Privacy Laws .” The scope and enforcement of each of these laws is not always certain and is subject to legislative, judicial or prosecutorial changes.
For more information on these laws and regulations see the section entitled “ Business – Government Regulation and Product Approval – Other Healthcare and Privacy Laws. ” The scope and enforcement of each of these laws is not always certain and is subject to legislative, judicial or prosecutorial changes.
Public perception and related media coverage of potential therapy-related efficacy or safety issues, including adoption of new therapeutics or novel approaches to treatment, as well as ethical concerns related specifically to genome editing and CRISPR/Cas9, may adversely influence the willingness of subjects to participate in clinical trials, or if any therapeutic is approved, of physicians and patients to accept these novel and personalized treatments.
Public perception and related media coverage of potential therapy-related efficacy or safety issues, including adoption of new therapeutics or novel approaches to treatment, as well as ethical concerns related specifically to genome editing and CRISPR-based therapies, may adversely influence the willingness of subjects to participate in clinical trials, or if any therapeutic is approved, of physicians and patients to accept these novel and personalized treatments.
If these patents are deemed valid and cover our product candidates or related activities, we could be prevented from developing and commercializing all or some of our product candidates unless we license the relevant intellectual property or avoid it.
If these patents are deemed valid and cover our product candidates or related activities, we could be prevented from developing and/or commercializing all or some of our product candidates, or the resulting products, unless we license the relevant intellectual property or avoid it.
Any security breaches that lead to unauthorized access, use, or disclosure of personal information, including personal information regarding our employees or current or future clinical trial participants, could harm our reputation, require us to comply with onerous legal requirements under laws and regulations that protect the privacy and security of personal information, and subject us to significant liability including fines, litigation, and loss of current and future business.
Any security incidents, compromises or breaches that lead to unauthorized access, use, or disclosure of personal information, including personal information regarding our employees or current or future clinical trial participants, could harm our reputation, require us to 63 comply with onerous legal requirements under laws and regulations that protect the privacy and security of personal information, and subject us to significant liability including fines, litigation, and loss of current and future business.
Any of these manufacturing and supply issues or delays could restrict our ability to meet clinical or market demand for our products, and be costly to us and otherwise harm our business, financial condition, results of operations and prospects.
Any of these manufacturing and supply issues or delays could restrict our ability to meet clinical or market demand for our product candidates or products and be costly to us and otherwise harm our business, financial condition, results of operations and prospects.
See the above risk factor titled “ Third party claims of intellectual property infringement against us, our licensors or our collaborators may prevent or delay our product discovery and development efforts .” Such challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to practice the invention or stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products.
See the above risk factor entitled “ Third party claims of intellectual property infringement against us, our licensors or our collaborators may prevent or delay our product discovery, research, development and/or commercialization efforts .” Such challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to practice the invention or stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products.
Although one CRISPR/Cas9-edited ex vivo therapy has been recently approved in the United States (“U.S.”) and European Union (“EU”), no genome editing in vivo therapy has been approved in the U.S., EU countries or other key jurisdictions, and the potential to successfully obtain approval for any of our CRISPR/Cas9 product candidates remains unproven.
Although one CRISPR/Cas9-edited ex vivo therapy has been approved in the United States (“U.S.”) and European Union (“EU”), no genome editing in vivo therapy has been approved in the U.S., EU countries or other key jurisdictions, and the potential to successfully obtain approval for any of our CRISPR/Cas9 product candidates remains uncertain.
In the U.S., the principal decisions about reimbursement for new medicines are typically made by the Centers for Medicare & Medicaid Services (“CMS”), an agency within the U.S. Department of Health and Human Services. CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare, and private payors often follow CMS’s coverage decisions.
In the U.S., the principal decisions about reimbursement for new medicines are typically made by the CMS, an agency within the U.S. Department of Health and Human Services. CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare, and private payors often follow CMS’s coverage decisions.
We have received orphan drug designation for NTLA-2001 and NTLA-2002 and may in the future seek orphan drug designation for some of our other product candidates, but we may be unable to obtain such designations or to maintain the benefits associated with orphan drug status, including market exclusivity, which may cause our revenue, if any, to be reduced.
We have received orphan drug designation for nex-z and NTLA-2002 and may in the future seek orphan drug designation for some of our other product candidates, but we may be unable to obtain such designations or to maintain the benefits associated with orphan drug status, including market exclusivity, which may cause our revenue, if any, to be reduced.
Therapeutic applications of genome editing technologies, and CRISPR/Cas9 in particular, for both in vivo products and ex vivo products, are unproven and must undergo rigorous clinical trials and regulatory review before receiving marketing authorization.
Therapeutic applications of genome editing technologies, and CRISPR/Cas9 in particular, for both in vivo products and ex vivo products, are uncertain and must undergo rigorous clinical trials and regulatory review before receiving marketing authorization.
There can be no assurance we will be successful in solving any or all of these issues. With regards to CRISPR/Cas9-based therapies specifically, we are in clinical-stage development for NTLA-2001 and NTLA-2002 and advancing towards clinical testing for our other in vivo and ex vivo product candidates.
There can be no assurance we will be successful in solving any or all of these issues. With regards to CRISPR/Cas9-based therapies specifically, we are in clinical-stage development for nex-z and NTLA-2002 and advancing towards clinical testing for our other in vivo and ex vivo product candidates.
Because patent rights are granted jurisdiction-by-jurisdiction, our freedom to practice certain technologies, including our ability to research, develop and commercialize our product candidates, may differ by country. Third parties may assert that we infringe their patents or that we are otherwise employing their proprietary technology without authorization, and may sue us.
Because patent rights are granted jurisdiction-by-jurisdiction, our freedom to practice certain technologies, including our ability to research, develop and/or commercialize our product candidates, or the resulting products, may differ by country. Third parties may assert that we infringe their patents or that we are otherwise employing their proprietary technology without authorization and may sue us.
Risks Related to Data and Privacy Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our operations and development efforts. We are increasingly dependent upon information technology systems, infrastructure, and data to operate our business.
Risks Related to Data and Privacy Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches, incidents, or compromises, which could result in a disruption of our operations and development efforts. We are increasingly dependent upon information technology systems, infrastructure, and data to operate our business.
Risks Related to Government Regulation Risks Related to Obtaining Regulatory Approval While the regulatory framework for approval of gene therapy including genome editing products exists, the limited precedent for genome-edited products makes the regulatory approval process potentially more unpredictable and we may experience significant delays in the clinical development and regulatory approval, if any, of our product candidates.
Risks Related to Government Regulation Risks Related to Obtaining Regulatory Approval While the regulatory framework exists for approval of gene therapy products, including genome editing products, the limited precedent for genome editing products make the regulatory approval process potentially more unpredictable and we may experience significant delays in the clinical development and regulatory approval, if any, of our product candidates.
In particular, our success will depend upon physicians who specialize in the treatment of diseases targeted by our product candidates prescribing treatments that involve the use of our product candidates in lieu of, or in addition to, existing treatments with which they are more familiar and for which greater clinical data may be available.
In particular, our success will depend upon physicians who specialize in the treatment of diseases targeted by our product candidates prescribing our product candidates in lieu of, or in addition to, existing treatments with which they are more familiar and for which greater clinical data may be available.
A variety of factors will influence whether our product candidates are accepted in the market, including, for example: • the clinical indications for which our product candidates are approved; • the potential and perceived advantages of our product candidates over alternative treatments; • the incidence and severity of any side effects, including any unintended deoxyribonucleic acid (“DNA”) changes; • product labeling or product insert requirements of the FDA or other regulatory authorities; • limitations or warnings contained in the labeling approved by the FDA or other regulatory authorities; • the timing of market introduction of our product candidates; • availability or existence of competitive products; • the cost of treatment in relation to alternative treatments; • the amount of upfront costs or training required for healthcare providers to administer our product candidates; • the availability of adequate coverage, reimbursement and pricing by government authorities and other third party payors; 48 • patients’ ability to access healthcare providers capable of delivering our product candidates; • patients’ willingness and ability to pay out-of-pocket in the absence of coverage and reimbursement by government authorities and other third party payors; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; • any restrictions on the use of our product candidates together with other medications; • interactions of our product candidates with other medicines patients are taking; • potential adverse events for any products developed, or negative interactions with regulatory agencies, by us or others in the gene therapy and genome editing fields; and • the effectiveness of our sales and marketing efforts and distribution support.
A variety of factors will influence whether our product candidates are accepted in the market, including, for example: • the clinical indications for which our product candidates are approved; • the potential and perceived advantages of our product candidates over alternative treatments; • the incidence and severity of any side effects, including any unintended deoxyribonucleic acid (“DNA”) changes; • product labeling or product insert requirements of the FDA or other regulatory authorities; • limitations or warnings contained in the labeling approved by the FDA or other regulatory authorities, which may include warnings or other information about possible unintended DNA changes; • the timing of market introduction of our product candidates; • availability or existence of competitive products; • the cost of treatment in relation to alternative treatments; • the amount of upfront costs or training required for healthcare providers to administer our product candidates, which may include availability of adequate facilities and equipment; • the availability of adequate coverage, reimbursement and pricing by government authorities and other third party payors; • patients’ ability to access healthcare providers capable of delivering our product candidates; • patients’ willingness and ability to pay out-of-pocket in the absence of coverage and reimbursement by government authorities and other third party payors; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; 40 • relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; • any restrictions on the use of our product candidates together with other medications; • interactions of our product candidates with other medicines patients are taking; • potential adverse events for any products developed, or negative interactions with regulatory agencies, by us or others in the gene therapy and genome editing fields; and • the effectiveness of our sales and marketing efforts and distribution support.
For more information on coverage and reimbursement see the section entitled “Business – Government Regulation and Product Approval – Coverage and Reimbursement . ” In the U.S. and some other jurisdictions, patients generally rely on third party payors to reimburse all or part of the costs associated with their treatment.
For more information on coverage and reimbursement see the section entitled “ Business – Government Regulation and Product Approval – Coverage and Reimbursement. ” 67 In the U.S. and some other jurisdictions, patients generally rely on third party payors to reimburse all or part of the costs associated with their treatment.
To the extent there was a change in control during 2023, our tax attributes could be subject to limitation. We may experience ownership changes in the future.
To the extent there was a change in control during 2023 and 2024, our tax attributes could be subject to limitation. We may experience ownership changes in the future.
Under Sections 382 and 383 of the Code, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may be limited.
Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended (the “Code”), if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may be limited.
For example, we are not permitted to market any drug or biological product, including in vivo products or engineered cell therapies, until we receive regulatory approval from the relevant regulatory agency, such as the FDA in the U.S. or EMA in the EU.
For example, we are not permitted to market any drug or biological product, including in vivo products or engineered cell therapies, until we receive regulatory approval from the relevant regulatory agency, such as the FDA in the U.S. or European Commission in the EU.
Further, we may encounter problems achieving adequate quantities and quality of clinical grade materials that meet the FDA or other relevant regulatory agency’s applicable standards or our specifications with consistent and acceptable production yields and costs.
Further, we may encounter problems achieving adequate quantities and quality of clinical (or, if approved commercial) grade materials that meet the FDA or other relevant regulatory agency’s applicable standards or our specifications with consistent and acceptable production yields and costs.
Risks Related to Future Financial Condition Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of stockholders and could cause our stock price to fall.
Risks Related to Future Financial Condition Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans and “at-the-market” offerings, could result in additional dilution of the percentage ownership of stockholders and could cause our stock price to fall.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeWe maintain a CSIRP that is designed to guide our incident response process for cybersecurity incidents that could affect our systems, network, or data. The CSIRP identifies the individuals responsible for developing, maintaining, and following appropriate procedures to identified cybersecurity incidents.
Biggest changeWe employ third parties, including assessors, consultants and auditors, in our cyber risk management program as appropriate, e.g., training, assessment, auditing, benchmarking, and penetration testing. Our CSIRP is designed to guide our incident response process for cybersecurity incidents that could affect our systems, network, or data.
Our cybersecurity risk management program includes a number of components, including but not limited to a Cybersecurity Incident Response Plan (“CSIRP”), annual cybersecurity awareness training for our employees, vendor risk management, regular system maintenance including application of security patches as appropriate, regular penetration test and security assessments and implementation of enhancements to security measures used to protect our systems and data.
Our cybersecurity risk management program includes a number of components, including but not limited to a Cybersecurity Incident Response Plan (“CSIRP”), annual cybersecurity awareness training for our employees, security assessments, vendor risk management, regular system maintenance including application of security patches as appropriate, regular penetration testing and implementation of enhancements to security measures used to protect our systems and data.
For more information about the cybersecurity risks we face, see the risk factor entitled “Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our operations and development efforts” in Item 1A-Risk Factors.
For more information about the cybersecurity risks we face, see the risk factor entitled “Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches, incidents or compromises, which could result in a disruption of our operations and development efforts” in Item 1A. Risk Factors.
Item 1C. C ybersecurity Risk management and strategy: We face a number of cybersecurity risks in connection with our business and recognize the growing threat within the general marketplace and our industry.
Item 1C. Cybersecurity Risk management and strategy: We face a number of cybersecurity risks in connection with our business and recognize the growing threat within the general marketplace and our industry.
The Audit Committee, with assistance from our management, including our Head of IT, periodically reports to the full Board of Directors to inform them of potential cyber risks and threats, the status of projects to further develop our information security systems, and the emerging cybersecurity threat landscape.
The Audit Committee, with assistance from our management, including our Head of Information Technology (“IT”), periodically reports to the full Board of Directors to inform them of potential cybersecurity risks and threats, the status of projects to further develop our information security systems, and the emerging cybersecurity threat landscape .
To help the Company address these risks, we have implemented a cybersecurity risk management program that is informed by recognized industry standards and frameworks and incorporates elements of the same, including elements of the National Institute of Standards and Technology Cybersecurity Framework.
To help the Company address these risks, we have implemented a cybersecurity risk management program that is informed by recognized industry standards and frameworks and incorporates elements of the same, including elements of the National Institute of Standards and Technology Cybersecurity Framework. Our cybersecurity risk management program is integrated within our enterprise risk management program.
We periodically test our CSIRP using tabletop exercises with the goal of improving our processes and preparedness. 88 Risks from cybersecurity threats have not to date materially affected us, including our business strategy, results of operations or financial condition.
Risks from cybersecurity threats have not to date materially affected us , including our business strategy, results of operations or financial condition.
Our Head of IT also provides regular updates on our cybersecurity risk to our executive leadership team and other management committees responsible for IT and cybersecurity risk management.
The Head of IT role is currently held by an individual who has close to twenty years of professional IT management experience in the life sciences industry. Our Head of IT also provides regular updates on 75 our cybersecurity risk to our executive leadership team and other management committees responsible for IT and cybersecurity risk management.
Removed
Our Head of IT is responsible for strategic leadership of our cybersecurity risk management program. The Head of IT role is currently held by an individual who has approximately eighteen years of professional IT management experience.
Added
The CSIRP identifies the individuals responsible for developing, maintaining, and following appropriate procedures related to identified cybersecurity incidents, including a framework for identifying and addressing material cybersecurity incidents. We periodically test our CSIRP using tabletop exercises with the goal of improving our processes and preparedness.
Added
Our Head of IT has primary responsibility for day-to-day management of our cybersecurity risk management program , including leading a dedicated team of IT professionals to monitor and assess cybersecurity risks, and is responsible for strategic leadership of our cybersecurity risk management program.
Added
Under our CSIRP and other applicable policies and procedures, we have established a framework for responding to cybersecurity incidents based on severity of the incident, which includes escalation to our executive leadership team and other management committees and assessment of materiality of cybersecurity incidents individually and in the aggregate .

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeIn March 2020, we entered into an agreement to lease approximately 39,000 square feet of office and laboratory space at 281 Albany Street in Cambridge, Massachusetts with an initial term of ten years and an option to extend the lease for two successive five-year terms.
Biggest changeIn addition, we lease approximately 15,200 square feet of office and laboratory space at 130 Brookline Street in Cambridge, Massachusetts, which expires in 2031, approximately 39,000 square feet of office and laboratory space at 281 Albany Street in Cambridge, Massachusetts, which expires in 2030 with an option to extend the lease for two successive five-year terms, approximately 62,000 square feet of office and laboratory space at 640 Memorial Drive, Cambridge, Massachusetts, which expires in 2027, approximately 14,000 square feet of office space at 17 Tudor Street in Cambridge, Massachusetts, which expires in 2025 and approximately 38,000 square feet of office and laboratory space at 730 Main Street, Cambridge, Massachusetts, which expires in 2032 with an option to extend the lease for one five-year term.
Item 2. Pr operties Our headquarters are located at 40 Erie Street in Cambridge, Massachusetts, where we occupy approximately 65,000 square feet of office and laboratory space. We have a ten-year lease agreement expiring in September 2026, with an option to extend the term of the lease for an additional three years.
Our headquarters are located at 40 Erie Street in Cambridge, Massachusetts, where we occupy approximately 65,000 square feet of office and laboratory space, which expires in 2026, with an option to extend the term of the lease for an additional three years.
In February 2022, we entered into an agreement to lease approximately 140,000 square feet of office, general laboratory and manufacturing space at 840 Winter Street, Waltham Massachusetts, which will provide us with the ability to manufacture products in a good manufacturing practice (“GMP”) compliant facility in the future.
We have subleased approximately 13,000 square feet of the property at 730 Main Street for office and laboratory use through March 2026. We also lease approximately 140,000 square feet of office, general laboratory and manufacturing space at 840 Winter Street, Waltham, Massachusetts. In February 2025, we entered into a Second Amendment to Lease (the “Winter Street Amendment”).
Removed
In addition, we lease approximately 15,200 square feet of office and laboratory space at 130 Brookline Street in Cambridge, Massachusetts, which expires in 2031.
Added
Item 2. Properties In aggregate, the Company leases approximately 370,000 square feet of real estate, including office, laboratory and manufacturing space in Cambridge, Massachusetts and the surrounding areas.
Removed
In July 2021, we entered into an agreement to lease approximately 14,000 square feet of office space at 17 Tudor Street in Cambridge, Massachusetts with an initial term of five years and an option to extend the lease for one three-year term.
Added
Pursuant to the Winter Street Amendment, the 840 Winter Street lease will terminate on or before June 30, 2028, as described in Note 16, “Subsequent Events.”
Removed
In January 2022, we entered into an agreement to lease approximately 38,000 square feet of office and laboratory space at 730 Main Street, Cambridge, Massachusetts with an initial term of ten years and an option to extend the lease for one five-year term.
Removed
We have subleased approximately 13,000 square feet of this property for office and laboratory use through March 2026.
Removed
This lease is expected to commence in the second half of 2024 with an initial term of twelve years and an option to extend the lease for two five-year terms.
Removed
In June 2022, we entered into an agreement to lease approximately 62,000 square feet of office and laboratory space at 640 Memorial Drive, Cambridge, Massachusetts with a term of five years, ending in August 2027.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeIn addition, litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. If we were unable to prevail in any such legal proceedings, our business, results of operations, liquidity and financial condition could be adversely affected. Item 4.
Biggest changeIn addition, litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. If we were unable to prevail in any such legal proceedings, our business, results of operations, liquidity and financial condition could be adversely affected. BlueAllele Corp. v. Intellia Therapeutics, Inc.
Mine Safe ty Disclosures Not applicable. 89 PART II
Mine Safety Disclosures Not applicable. 76 PART II
Added
On July 8, 2024, BlueAllele Corp. (“BlueAllele”) filed a complaint alleging infringement by Intellia of various patents in the U.S. District Court for the District of Delaware.
Added
Specifically, BlueAllele alleges that our experimentation, basic research, identification, optimization, manufacturing and/or use of bi-directional insertion template technology infringes the asserted patents and seeks, inter alia , unspecified compensatory damages and an injunction against the alleged infringing activities.
Added
On September 12, 2024, we filed a motion to dismiss the complaint, and on December 9, 2024, the court denied the motion to dismiss and discovery began. On January 6, 2025, we filed our answer and counterclaims, and BlueAllele filed a motion to dismiss our counterclaims on January 27, 2025.
Added
On February 21, 2025, the court substantially denied BlueAllele’s motion to dismiss, and granted the motion with respect to one counterclaim. Gonzalez v. Intellia Therapeutics, Inc. On February 11, 2025, a purported stockholder of the Company filed a lawsuit, captioned Gonzalez v. Intellia Therapeutics, Inc. , No. 1:25-cv-01353 (D. Mass.), in the U.S.
Added
District Court for the District of Massachusetts against the Company and certain of our officers on behalf of a putative class of stockholders who purchased Company shares from July 30, 2024 through January 8, 2025.
Added
The complaint alleges claims under Sections 10(b) and 20(a) and Rule 10b-5 of the Securities Exchange Act of 1934 (the “Exchange Act”) premised upon statements relating to the Company’s NTLA-3001 program and the demand for viral-based editing. The complaint seeks unspecified damages, interest, reasonable attorneys’ fees and other costs. We intend to defend vigorously against the claims. Item 4.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeItem 5. Market for the Registrant’s Common Equity, Related St ockholder Matters and Issuer Purchases of Equity Securities Our common stock is traded on the Nasdaq Global Market under the symbol “NTLA”. As of February 16, 2024, the number of holders of record of our common stock was 14.
Biggest changeItem 5. Market for the Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Our common stock is traded on the Nasdaq Global Market under the symbol “NTLA.” As of February 14, 2025, the number of holders of record of our common stock was 13.
Data for the Nasdaq Composite Index and the Nasdaq Biotechnology Index assume reinvestment of dividends. 90 The performance graph in this Item 5 is not deemed to be “soliciting material” or to be “filed” with the Securities and Exchange Commission for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or otherwise subject to the liabilities under that Section, and shall not be deemed incorporated by reference into any of our filings under the Securities Act of 1933 or the Securities Exchange Act of 1934, except to the extent we specifically incorporate it by reference into such a filing.
Data for the Nasdaq Composite Index and the Nasdaq Biotechnology Index assume reinvestment of dividends. 77 The performance graph in this Item 5 is not deemed to be “soliciting material” or to be “filed” with the Securities and Exchange Commission for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or otherwise subject to the liabilities under that Section, and shall not be deemed incorporated by reference into any of our filings under the Securities Act of 1933 or the Securities Exchange Act of 1934, except to the extent we specifically incorporate it by reference into such a filing.
Stock Performance Graph The following graph shows a comparison from December 31, 2018 through December 31, 2023, of the cumulative total return on an assumed investment of $100.00 in cash in our common stock, the Nasdaq Composite Index and the Nasdaq Biotechnology Index. Such returns are based on historical results and are not intended to suggest future performance.
Stock Performance Graph The following graph shows a comparison from December 31, 2019 through December 31, 2024, of the cumulative total return on an assumed investment of $100.00 in cash in our common stock, the Nasdaq Composite Index and the Nasdaq Biotechnology Index. Such returns are based on historical results and are not intended to suggest future performance.
Unregistered Sales of Equity Securities and Use of Proceeds None. Item 6. [R e served]. 91
Unregistered Sales of Equity Securities and Use of Proceeds None. Item 6. [Reserved]. 78

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeYear Ended December 31, Period-to- Percent 2023 2022 Period Change Change External development expenses by program: NTLA-2001 $ 54,454 $ 37,849 $ 16,605 44 % NTLA-2002 24,560 11,611 12,949 112 % NTLA-3001 17,312 11,506 5,806 50 % NTLA-5001 - 17,827 (17,827 ) -100 % Unallocated research and development expenses: Employee-related expenses 136,628 112,931 23,697 21 % Research materials and contracted services 60,726 74,834 (14,108 ) -19 % In-process research and development - 55,990 (55,990 ) -100 % Research milestone 874 - 874 - Facility-related expenses 53,141 37,618 15,523 41 % Stock-based compensation 82,211 56,279 25,932 46 % Other 5,163 3,534 1,629 46 % Total research and development expenses $ 435,069 $ 419,979 $ 15,090 4 % The increase in research and development expenses for the year ended December 31, 2023 compared to the year ended December 31, 2022 was primarily attributable to: • a $16.6 million increase in external costs related to the development of NTLA-2001, our lead product candidate, primarily due to an increase in spend on drug components and contracted services; • a $12.9 million increase in external costs related to the development of NTLA-2002, primarily due to an increase in spend on drug components, contracted services and consulting services; • a $5.8 million increase in external costs related to NTLA-3001, primarily related to an increase in spend on drug components and consulting and professional services, offset in part by a decrease in spend on contracted services; • a $17.8 million decrease in external costs related to the development of NTLA-5001, as we discontinued this program as part of our pivot to an allogeneic pipeline; • a $23.7 million increase in employee-related expenses, primarily driven by the increase in personnel growth to support our lead programs; • a $14.1 million decrease in research materials and contracted services primarily driven by a decrease in drug component expenses and contracted services related to early stage programs; • a $56.0 million decrease in in-process research and development expense related to the acquisition of Rewrite Therapeutics, Inc. in the first half of 2022; • a $15.5 million increase in facility-related expenses primarily related to rent, depreciation, maintenance and services, and technology expense allocated to research and development; and • a $25.9 million increase in stock-based compensation driven by increases in employee headcount in 2023 compared to 2022.
Biggest changeResearch and Development Research and development expenses increased by $31.2 million to $466.3 million during the year ended December 31, 2024, as compared to $435.1 million during the year ended December 31, 2023. 80 The following table summarizes our research and development expenses, together with the changes in those items in dollars and the respective percentages of change: Year Ended December 31, Period-to- Percent 2024 2023 Period Change Change (In thousands) External development expenses by program: Nex-z $ 69,793 $ 54,454 $ 15,339 28 % NTLA-2002 42,173 24,560 17,613 72 % NTLA-3001 8,709 17,312 (8,603 ) -50 % Unallocated research and development expenses: Employee-related expenses 127,383 136,628 (9,245 ) -7 % Research materials and contracted services 60,661 60,726 (65 ) 0 % Rewrite research milestone - 874 (874 ) -100 % Facility-related expenses 59,397 53,141 6,256 12 % Stock-based compensation 94,230 82,211 12,019 15 % Other 3,965 5,163 (1,198 ) -23 % Total research and development expenses $ 466,311 $ 435,069 $ 31,242 7 % The increase in research and development expenses for the year ended December 31, 2024 compared to the year ended December 31, 2023 was primarily attributable to: • a $15.3 million increase in external costs related to the development of nexiguran ziclumeran (“nex-z”, also referred to as NTLA-2001), one of our lead product candidates, primarily due to an increase in spend on contracted services and consulting fees, offset in part by a decrease in drug components; • a $17.6 million increase in external costs related to the development of NTLA-2002, primarily due to an increase in spend on drug components, contracted services and consulting fees; • an $8.6 million decrease in external costs related to NTLA-3001, primarily related to initial manufacturing activities in 2023, offset in part by an increase in spend on contracted services; • a $9.2 million decrease in employee-related expenses, primarily driven by a workforce reduction in January 2024; • a $6.3 million increase in facility-related expenses primarily related to depreciation, facility maintenance costs, technology expense allocated to research and development, and rent; and • a $12.0 million increase in stock-based compensation.
Research and Development Research and development costs consist of expenses incurred in performing research and development activities, such as compensation and benefits, which includes stock-based compensation, for full-time research and development employees, allocated facility-related expenses, overhead expenses, license and milestone fees, contract research, development and manufacturing services, clinical trial costs and other related costs.
Research and Development Research and development expenses consist of expenses incurred in performing research and development activities, such as compensation and benefits, which includes stock-based compensation, for full-time research and development employees, allocated facility-related expenses, overhead expenses, license and milestone fees, contract research, development and manufacturing services, clinical trial costs and other related costs.
Our ability to generate revenue and achieve profitability depends significantly on our success in many areas, including: developing our delivery technologies and our CRISPR/Cas9 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; 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; 96 maintaining, protecting, and expanding our portfolio of IP rights, including patents, trade secrets, and know-how; and attracting, hiring, and retaining qualified personnel.
Our ability to generate revenue and achieve profitability depends significantly on our success in many areas, including: developing our delivery technologies and our CRISPR/Cas9 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; 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 82 collaborators and licensors; maintaining, protecting, and expanding our portfolio of IP rights, including patents, trade secrets, and know-how; and attracting, hiring, and retaining qualified personnel.
We base our expenses related to preclinical 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.
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.
To achieve this core principle, we apply the following five steps: (i) identify the contract with the customer; (ii) identify the performance obligations in the contract; (iii) determine the 98 transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when or as we satisfy a performance obligation.
To achieve this core principle, we apply the following five steps: (i) identify the contract with the customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when or as we satisfy a performance obligation.
We believe the critical accounting policies used in the preparation of our consolidated financial statements which require significant estimates and judgments are as follows: Revenue Recognition We recognize revenue in accordance with Accounting Standards Update (“ASU”) 2014-09, Revenue from Contracts with Customers (Topic 606) and its related amendments (collectively known as Accounting Standard Codification (“ASC”) 606 (“ASC 606”).
We believe the critical accounting policies used in the preparation of our consolidated financial statements which require significant estimates and judgments are as follows: Revenue Recognition We recognize revenue in accordance with Financial Accounting Standards Board (“FASB”) Accounting Standards Update (“ASU”) 2014-09, Revenue from Contracts with Customers (Topic 606) and its related amendments (collectively known as Accounting Standard Codification (“ASC”) 606 (“ASC 606”).
Information pertaining to fiscal year 2021 was included in our Annual Report on Form 10-K for the year ended December 31, 2022 under Part II, Item 7, “Management’s Discussion and Analysis of Financial Position and Results of Operations,” which was filed with the Securities and Exchange Commission (the “SEC”) on February 23, 2023. Management Overview Intellia Therapeutics, Inc.
Information pertaining to fiscal year 2022 was included in our Annual Report on Form 10-K for the year ended December 31, 2023 under Part II, Item 7, “Management’s Discussion and Analysis of Financial Position and Results of Operations,” which was filed with the Securities and Exchange Commission (the “SEC”) on February 22, 2024. Management Overview Intellia Therapeutics, Inc.
Outlook Based on our research and development plans and our expectations related to the progress of our programs, we expect that our cash, cash equivalents and marketable securities as of December 31, 2023, as well as research and cost reimbursement funding from our collaboration agreements will enable us to fund our ongoing operating expenses and capital expenditure requirements into mid-2026, excluding any potential milestone payments or extension fees that could be earned and distributed under our collaboration agreements or any strategic use of capital not currently in the base case planning assumptions.
Outlook Based on our research and development plans and our expectations related to the progress of our programs, we expect that our cash, cash equivalents and marketable securities as of December 31, 2024, as well as research and cost reimbursement funding from our collaboration agreements, will enable us to fund our ongoing operating expenses and capital expenditure requirements into the first half of 2027, excluding any potential milestone payments or extension fees that could be earned and distributed under our collaboration agreements or any strategic use of capital not currently in the base case planning assumptions.
Estimates of stock-based compensation expense for an award with a performance condition are based on our assessment of the probability that the performance condition will be achieved. Our stock price is a key input that will drive the grant date fair value of the equity awards.
Estimates of stock-based compensation expense for an award with a performance condition are based on our assessment of the probability that the performance condition will be achieved, which requires significant judgment. Our stock price is a key input that will drive the grant date fair value of the equity awards.
Net cash provided by financing activities Net cash provided by financing activities of $130.3 million during the year ended December 31, 2023 is primarily due to the receipt of $119.8 million in net proceeds from at-the-market offerings, $6.6 million in cash received from the exercise of stock options and $3.9 million in cash received from the issuance of shares through our employee stock purchase plan.
Net cash provided by financing activities of $130.3 million during the year ended December 31, 2023 includes $119.8 million in net proceeds from at-the-market offerings, $6.6 million in cash received from the exercise of stock options and $3.9 million in cash received from the issuance of shares through our employee stock purchase plan.
Critical Accounting Policies and Use of Estimates Our management’s discussion and analysis of financial condition and results of operations is based upon our consolidated financial statements, which have been prepared in accordance with accounting principles generally accepted in the U.S.
Critical Accounting Policies and Use of Estimates Our management’s discussion and analysis of financial condition and results of operations is based upon our consolidated financial statements, which have been prepared in accordance with U.S. GAAP.
Contractual and Other Obligations We have entered into arrangements that contractually obligate us to make payments that will affect our liquidity and cash flows in future periods . 97 Property Leases - Commenced As of December 31, 2023, our contractual commitments for leases were $146.5 million, which will be paid over the term of such leases.
Contractual Obligations We have entered into arrangements that contractually obligate us to make payments that will affect our liquidity and cash flows in future periods. Property Leases As of December 31, 2024, our total undiscounted future minimum lease payments for our property leases that have commenced were $294.8 million, which will be paid over the term of such leases.
Except for these sources of funding, we will not have any committed external source of liquidity. To the extent that we raise additional capital through the future sale of equity, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing stockholders.
To the extent that we raise additional capital through the future sale of equity, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing stockholders.
Cash Flows The following is a summary of cash flows for the years ended December 31, 2023 and 2022: Year Ended December 31, 2023 2022 (In thousands) Net cash used in operating activities $ (394,086 ) $ (333,287 ) Net cash (used in) provided by investing activities (31,347 ) 160,309 Net cash provided by financing activities 130,323 582,955 Net cash used in operating activities Net cash used in operating activities of $394.1 million during the year ended December 31, 2023 primarily consists of a net loss of $481.2 million, further reduced by changes in operating assets and liabilities of $52.5 million, including the receipt of $18.7 million in payments from our collaboration partners during that period and offset in part by non-cash charges of stock-based compensation of $134.1 million, loss on equity method investment of $22.3 million and depreciation of $9.0 million.
Net cash used in operating activities of $394.1 million during the year ended December 31, 2023 primarily consists of a net loss of $481.2 million, further reduced by changes in operating assets and liabilities of $52.5 million, including the receipt of $18.7 million in payments from our collaboration partners during that period and offset in part by non-cash charges of stock-based compensation of $134.1 million, loss on equity method investment of $22.3 million and depreciation of $9.0 million.
Liquidity and Capital Resources Since our inception through December 31, 2023, we have raised an aggregate of $2,534.1 million to fund our operations through our collaboration agreements, our initial public offering and concurrent private placements, follow-on public offerings, at-the-market offerings and the sale of convertible preferred stock.
Liquidity and Capital Resources Since our inception through December 31, 2024, we have funded our operations through our initial public offering and concurrent private placements, follow-on public offerings, our collaboration agreements, at-the-market offerings and the sale of convertible preferred stock.
Also included in general and administrative expenses are allocated facility-related costs not otherwise included in research and development expenses, travel expenses and professional fees for auditing, tax and legal services, including IP-related legal services, and other consulting fees and expenses. 92 Other Income (Expense), Net Other income (expense) consists of interest income earned on our cash, cash equivalents, restricted cash equivalents and marketable securities, loss from equity method investment and change in fair value of contingent consideration.
Also included in general and administrative expenses are allocated facility-related costs not otherwise included in research and development expenses, travel expenses and professional fees for auditing, tax and legal services, including IP-related legal services, and other consulting fees and expenses. 79 Other Income (Expense), Net During the year ended December 31, 2024, other income (expense), net consists of interest income earned on our cash, cash equivalents, restricted cash equivalents and marketable securities and change in the fair value of our investments.
During the year ended December 31, 2022, we issued 3,395,339 shares of our common stock, in a series of sales, at an average price of $57.43 per share, in accordance with the 2022 Sale Agreement for aggregate net proceeds of $189.0 million, after payment of cash commissions and legal, accounting and other fees in connection with the sales.
During the year ended December 31, 2024, we issued 7,004,370 shares of our common stock, in a series of sales, at an average price of $25.68 per share, in accordance with the 2022 Sale Agreement, as amended, for aggregate net proceeds of $174.8 million, after payment of cash commissions and approximately $0.3 million related to legal, accounting and other fees in connection with the sales.
Stock-based compensation expense is recognized on a straight-line basis over the requisite service period of the awards and is adjusted for pre-vesting forfeitures in the period in which the forfeitures occur. For equity awards that have a performance or market condition, we recognize stock-based compensation expense using the accelerated attribution method.
For awards with service conditions only, we recognize stock-based compensation expense on a straight-line basis over the requisite service period. For equity awards that have a performance or market condition, we recognize stock-based compensation expense using the accelerated attribution method.
At-the-Market Offering Programs 2019 Sale Agreement In August 2019, we entered into an Open Market Sale Agreement (the “2019 Sale Agreement”) with Jefferies LLC (“Jefferies”), under which Jefferies was able to offer and sell, from time to time in “at-the-market” offerings, shares of our common stock having aggregate gross proceeds of up to $150.0 million.
As of December 31, 2024, we had $861.7 million in cash, cash equivalents and marketable securities. 81 At-the-Market Offering Programs 2022 Sale Agreement In 2022, we entered into an Open Market Sale Agreement (the “2022 Sale Agreement”) with Jefferies LLC (“Jefferies”), under which Jefferies is able to offer and sell, from time to time in “at-the-market” offerings, shares of our common stock having aggregate gross proceeds of up to $400.0 million.
As of December 31, 2023, our revenue recognized is solely related to collaboration agreements with third parties which are either within the scope of ASC 606, under which we license certain rights to our product candidates to third parties, or within the scope of ASC 808, Collaborative Arrangements (“ASC 808”) if it involves a joint operating activity pursuant to which we are an active participant and are exposed to significant risks and rewards with respect to the arrangement.
We only apply the five-step model to contracts when 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. 84 As of December 31, 2024, our revenue recognized is solely related to collaboration agreements with third parties which are either within the scope of ASC 606, under which we license certain rights to our product candidates to third parties, or within the scope of ASC 808, Collaborative Arrangements (“ASC 808”) if it involves a joint operating activity pursuant to which we are an active participant and are exposed to significant risks and rewards with respect to the arrangement.
Financial Overview Collaboration Revenue Our revenue consists of collaboration revenue, including amounts recognized related to upfront technology access payments for licenses, technology access fees, research materials shipped, research funding and milestone payments earned under our collaboration and license agreements.
For more information regarding our business, mission and pipeline, see above sections in Part I entitled “ Overview, ” “ Strategy ” and “ Our Pipeline. ” Financial Overview Collaboration Revenue Our revenue consists of collaboration revenue, including amounts recognized related to upfront technology access payments for licenses, technology access fees, research materials shipped, research funding and milestone payments earned under our license and collaboration agreements.
We are eligible to earn a significant amount of milestone payments and royalties, in each case, on a per-product basis under our collaborations with SparingVision SAS (“SparingVision”) and ONK Therapeutics, Ltd. (“ONK”), on a per-target basis under our collaboration with Regeneron Pharmaceuticals, Inc. (“Regeneron”) and upon achievement of certain events under our collaboration with Kyverna Therapeutics, Inc. (“Kyverna”).
Additionally, we are eligible to earn milestone payments and royalties, in each case, on a per-product basis under our collaborations with SparingVision SAS (“SparingVision”), ONK Therapeutics, Ltd. (“ONK”) and ReCode Therapeutics, Inc.
The fair value of market-based restricted stock units is determined using a Monte Carlo simulation model, which uses multiple input variables to determine the probability of satisfying the market condition requirements.
Forfeitures are recorded as they occur. 85 The fair value of market-based restricted stock units and performance-based restricted stock units with a Total Shareholder Return (“TSR”) multiplier are determined using a Monte Carlo simulation model, which uses multiple input variables to determine the probability of satisfying the market condition requirements.
Net cash (used in) provided by investing activities During the year ended December 31, 2023, our investing activities used cash of $31.3 million primarily due to $904.5 million of marketable securities purchased and $14.0 million in cash for the purchase of property and equipment, offset in part by $887.1 million in marketable securities maturing.
The increase in the year ended December 31, 2024 is primarily due to $131.3 million in marketable securities that matured (net of purchases), offset in part by $5.8 million in cash used for the purchase of property and equipment. During the year ended December 31, 2023 we used cash of $31.3 million in investing activities.
Net cash provided by financing activities of $583.0 million during the year ended December 31, 2022 is primarily due to the receipt of $337.9 million in net proceeds from a follow-on offering of our common stock, $227.9 million in net proceeds from at-the-market offerings, $14.5 million in cash received from the exercise of stock options and $2.6 million in cash received from the issuance of shares through our employee stock purchase plan.
Net cash provided by financing activities Net cash provided by financing activities of $185.7 million during the year ended December 31, 2024 includes $176.9 million in net proceeds from at-the-market offerings, $5.9 million in cash received from the exercise of stock options and $3.0 million in cash received from the issuance of shares through our employee stock purchase plan.
We do not include any potential future pass-through milestone payments or royalty payments we may be required to make under our existing license agreements or the merger agreement related to our acquisition of Rewrite due to the uncertainty of the occurrence of the events requiring payment under those agreements. These payments are not reflected in the disclosures above.
These contracts are generally cancelable at any time by us upon prior written notice. We do not include any potential future pass-through milestone payments or royalty payments we may be required to make under our existing license agreements or the merger agreement related to our acquisition of Rewrite Therapeutics, Inc.
We have based this estimate on current assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect. In January 2024, following an internal strategic review, we announced an effort to streamline company-wide operations to further focus resources on key strategic priorities and programs.
We have based this estimate on current assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect.
General and Administrative General and administrative expenses increased by $26.2 million to $116.5 million during the year ended December 31, 2023, compared to $90.3 million during the year ended December 31, 2022.
General and Administrative General and administrative expenses increased by $9.3 million to $125.8 million during the year ended December 31, 2024, compared to $116.5 million during the year ended December 31, 2023. This increase was primarily related to an increase in stock-based compensation of $8.2 million.
Comparison of Years Ended December 31, 2023 and 2022 The following table summarizes our results of operations for the years ended December 31, 2023 and 2022 (in thousands): Year Ended December 31, Period-to- 2023 2022 Period Change Collaboration revenue $ 36,275 $ 52,121 $ (15,846 ) Operating expenses: Research and development 435,069 419,979 15,090 General and administrative 116,497 90,306 26,191 Total operating expenses 551,566 510,285 41,281 Operating loss (515,291 ) (458,164 ) (57,127 ) Other income (expense), net: Interest income 49,832 8,542 41,290 Loss from equity method investment (15,633 ) (11,079 ) (4,554 ) Change in fair value of contingent consideration (100 ) (13,485 ) 13,385 Total other income (expense), net 34,099 (16,022 ) 50,121 Net loss $ (481,192 ) $ (474,186 ) $ (7,006 ) Collaboration Revenue Collaboration revenue decreased by $15.8 million to $36.3 million during the year ended December 31, 2023, as compared to $52.1 million during the year ended December 31, 2022.
Comparison of Year Ended December 31, 2024 and 2023 The following table summarizes our results of operations: Year Ended December 31, Period-to- 2024 2023 Period Change (In thousands) Collaboration revenue $ 57,877 $ 36,275 $ 21,602 Operating expenses: Research and development 466,311 435,069 31,242 General and administrative 125,829 116,497 9,332 Total operating expenses 592,140 551,566 40,574 Operating loss (534,263 ) (515,291 ) (18,972 ) Other income (expense), net: Interest income 47,807 49,832 (2,025 ) Change in fair value of investments, net (32,565 ) - (32,565 ) Loss from equity method investment - (15,633 ) 15,633 Change in fair value of contingent consideration - (100 ) 100 Total other income (expense), net 15,242 34,099 (18,857 ) Net loss $ (519,021 ) $ (481,192 ) $ (37,829 ) Collaboration Revenue Collaboration revenue increased by $21.6 million to $57.9 million during the year ended December 31, 2024, as compared to $36.3 million during the year ended December 31, 2023.
This decrease was primarily driven by a $10.3 million cumulative adjustment related to a contract modification resulting from Regeneron exercising a one-time option to extend the term of our technology collaboration for an additional two years. Refer to Note 9 to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for further details.
(“Regeneron”), offset by a $12.3 million decrease in revenue related to the AvenCell LCA. Refer to Note 9 to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for further details.
For additional information on our leases and timing of future payments refer to Note 12 of the consolidated financial statements included in this Annual Report on Form 10-K.
For additional information on our leases and timing of future payments refer to Note 11 of the consolidated financial statements included in this Annual Report on Form 10-K. 83 Other Obligations We enter into contracts in the normal course of business with various third parties for clinical trials, preclinical research studies, supply manufacturing and other services and products for operating purposes.
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 expense. 99 Stock-Based Compensation We measure employee stock-based compensation based on the grant date fair value of the equity awards using the Black-Scholes option pricing model.
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 expense. Stock-Based Compensation Our share-based compensation programs grant awards that have included stock options and restricted stock units. Grants are awarded to employees and non-employees, including directors.
Additionally, we are eligible to earn milestone payments and royalties, in each case, on a per-product basis under our collaborations with SparingVision and ONK, on a per-target basis under our collaboration with Regeneron, and upon achievement of certain events with Kyverna, subject to the provisions of our agreements with each of them.
(“ReCode”), on a per-target basis under our collaboration with Regeneron, and upon achievement of certain events with Kyverna, subject to the provisions of our agreements with each of them. Except for these sources of funding, we will not have any committed external source of liquidity.
(“we,” “us,” “our,” “Intellia,” or the “Company”) is a leading clinical-stage gene editing company, focused on developing potentially curative therapeutics using CRISPR/Cas9-based technologies.
(“we,” “us,” “our,” “Intellia,” or the “Company”) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. CRISPR is a gene editing technology which is also sometimes referred to as CRISPR/Cas or CRISPR/Cas9 when referring to the use of CRISPR technology with the Cas9 enzyme.
Follow-on Offering In December 2022, we closed an underwritten public offering of 7,532,751 shares of common stock, including the exercise in full of the underwriters’ option to purchase an additional 982,532 shares of common stock, at the public offering price of $45.80 per share, for aggregate net proceeds of $337.9 million, after deducting the underwriting discount, commissions and legal, accounting and other fees in connection with the sales. 95 Funding Requirements Our primary uses of capital are, and we expect will continue to be, research and development research materials and contracted services, clinical trial costs, compensation and related expenses, laboratory and office facilities, research supplies, legal and regulatory expenses, patent prosecution filing and maintenance costs for our licensed IP, milestone and royalty payments and general overhead costs.
Funding Requirements Our primary uses of capital are, and we expect will continue to be, research and development research materials and contracted services, clinical trial costs, compensation and related expenses, laboratory and office facilities, research supplies, legal and regulatory expenses, patent prosecution filing and maintenance costs for our licensed IP, milestone and royalty payments and general overhead costs.
We agreed to pay cash commissions of 3.0% of the gross proceeds of sales of common stock under the 2022 Sale Agreement. Through December 31, 2023 we have issued 7,518,163 shares of our common stock under the 2022 Sale Agreement.
To date through December 31, 2024 we have issued 14,522,533 shares of our common stock under the 2022 Sale Agreement, as amended.
During the year ended December 31, 2022, our investing activities provided net cash of $160.3 million primarily due to $647.6 million in marketable securities maturing, offset in part by $429.0 million of marketable securities purchased, $44.8 million in net cash for the acquisition of Rewrite, and $13.6 million in cash for the purchase of property and equipment.
The decrease in the year ended December 31, 2023 is primarily due to $17.4 million in marketable securities purchased (net of maturities) and $14.0 million in cash used for the purchase of property and equipment.
We agreed to pay cash commissions of 3.0% of the gross proceeds of sales of common stock under the 2019 Sale Agreement. Under the 2019 Sale Agreement, we issued 3,778,889 shares of our common stock.
In February 2024, we entered into an amendment to the 2022 Sale Agreement (the “2022 Sale Agreement, as amended”) to increase the size of the at-the-market offering program from $400.0 million to $750.0 million. We agreed to pay cash commissions of up to 3.0% of the gross proceeds of sales of common stock under the 2022 Sale Agreement, as amended.
Removed
CRISPR/Cas9, an acronym for C lustered, R egularly I nterspaced S hort P alindromic R epeats (“CRISPR”)/ C RISPR a ssociated 9 (“Cas9”), is a technology for genome editing, the process of altering selected sequences of genomic deoxyribonucleic acid (“DNA”).
Added
Since its inception, Intellia has focused on leveraging gene editing technology to develop novel, first-in-class medicines that address important unmet medical needs and advance the treatment paradigm for patients. Intellia’s deep scientific, technical and clinical development experience, along with its people, are helping set the standard for a new class of medicine.
Removed
For more information regarding our business, mission and pipeline, see above sections in Part I entitled “ Overview ”, “ Strategy ” and “ Our Pipeline ”.
Added
To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies.
Removed
Research and Development Research and development expenses increased by $15.1 million to $435.1 million during the year ended December 31, 2023, as compared to $420.0 million during the year ended December 31, 2022. 93 The following table summarizes our research and development expenses for the years ended December 31, 2023 and 2022, together with the changes in those items in dollars (in thousands) and the respective percentages of change.
Added
During the year ended December 31, 2023, other income (expense), net consisted of interest income earned on our cash, cash equivalents, restricted cash equivalents and marketable securities, loss from our equity method investment and change in fair value of contingent consideration.
Removed
During 2024, we expect research and development expenses to increase as we advance our global pivotal trials for NTLA-2001 and NTLA-2002, progress our NTLA-3001 program and nominate new development candidates.
Added
The increase in collaboration revenue during the year ended December 31, 2024 is primarily due to the recognition of $21.0 million of previously eliminated intra-entity profit under our license and collaboration agreement with AvenCell Therapeutics, Inc. (the “AvenCell LCA”) and a $12.8 million increase in revenue related to Regeneron Pharmaceuticals, Inc.
Removed
This increase was primarily related to an increase in employee-related expenses, including stock-based compensation of $16.7 million. 94 Other Income (Expense), Net The increase in other income (expense), net of $50.1 million is primarily related to a $41.3 million increase in interest income, driven by an increase in market rates, and a $13.4 million decrease in other expense related to the change in fair value of contingent consideration, offset in part by a $4.6 million increase in the loss from our equity method investment.
Added
Other Income (Expense), Net The decrease in other income (expense), net of $18.9 million is primarily related to $32.6 million in expense due to the change in fair value of our investments in Kyverna Therapeutics, Inc.
Removed
As of December 31, 2023, we had $1,012.1 million in cash, cash equivalents and marketable securities.
Added
(“Kyverna”) and AvenCell and a $2.0 million decrease in interest income, offset in part by a $15.6 million change related to our equity method loss recorded in the year ended December 31, 2023.
Removed
During the first quarter of 2022, we issued 579,788 shares of our common stock in a series of sales at an average price of $69.43 per share in accordance with the 2019 Sale Agreement, for aggregate net proceeds of $38.9 million after payment of cash commissions and legal, accounting and other fees in connection with the sales.
Added
As of December 31, 2024, $249.1 million in shares of common stock remain eligible for sale under the 2022 Sale Agreement, as amended.
Removed
The 2019 Sale Agreement expired in the third quarter of 2022. 2022 Sale Agreement In March 2022, we entered into an Open Market Sale Agreement (the “2022 Sale Agreement”) with Jefferies, under which Jefferies is able to offer and sell, from time to time in “at-the-market” offerings, shares of our common stock having aggregate gross proceeds of up to $400.0 million.
Added
During 2025, we expect our expenses to decrease compared to prior periods as a result of our recently announced strategic reorganization in January 2025, as we focus resources on high value programs within our pipeline, such as NTLA-2002 and nex-z, to ensure efficient execution, achieve near-term clinical milestones, and prepare for commercial launch.
Removed
During the year ended December 31, 2023, we issued 4,122,824 shares of our common stock, in a series of sales, at an average price of $30.57 per share, in accordance with the 2022 Sale Agreement for aggregate net proceeds of $121.9 million, after payment of cash commissions and legal, accounting and other fees in connection with the sales.
Added
Cash Flows The following is a summary of cash flows: Year Ended December 31, 2024 2023 (In thousands) Net cash used in operating activities $ (348,880 ) $ (394,086 ) Net cash provided by (used in) investing activities 125,567 (31,347 ) Net cash provided by financing activities 185,747 130,323 Net cash used in operating activities Net cash used in operating activities of $348.9 million during the year ended December 31, 2024 primarily consists of a net loss of $519.0 million, further reduced by the non-cash recognition of $21.0 million of previously eliminated intra-entity profit recorded within “collaboration revenue” and accretion of investment discounts and premiums of $17.8 million.
Removed
As of December 31, 2023, $2.1 million of these proceeds are included in “Prepaid expenses and other current assets” on our consolidated balance sheet, representing offerings with trade dates in December 2023 that were settled in January 2024.
Added
These decreases are offset in part by stock-based compensation of $154.3 million, $32.6 million in net adjustments to the fair value of our investments in Kyverna and AvenCell, net changes in operating assets and liabilities of $11.9 million and depreciation of $10.3 million.
Removed
During 2024, we expect our expenses to increase compared to prior periods in connection with our ongoing activities as we continue to develop our clinical programs and advance additional programs into clinical development.
Added
Net cash provided by (used in) investing activities During the year ended December 31, 2024, we added $125.6 million of net cash through investing activities.
Removed
Our ability to earn these milestone payments and the timing of achieving these milestones is dependent upon the outcome of our research and development activities and is uncertain at this time. Our rights to payments under our collaboration agreements are our only committed external source of funds.
Added
(“Rewrite”) due to the uncertainty of the occurrence of the events requiring payment under those agreements. These payments are not reflected in the disclosures above. In January 2023, a research milestone related to Rewrite was achieved and settled.
Removed
These changes resulted in a pause of select exploratory research-stage programs and a workforce reduction of approximately 15%.
Added
Stock-based compensation cost is measured at the grant date based on the fair value of the award and is recognized as an expense over the requisite service period. We measure employee stock-based compensation for stock options based on the grant date fair value of the equity awards using the Black-Scholes option pricing model.
Removed
Net cash used in operating activities of $333.3 million during the year ended December 31, 2022 primarily consists of a net loss of $474.2 million, further reduced by changes in operating assets and liabilities of $53.9 million, including the receipt of $10.7 million in payments from our collaboration partners during that period and offset in part by non-cash charges of stock-based compensation of $91.4 million, in-process research and development expense of $56.0 million, losses on equity method investment of $22.5 million and depreciation of $7.6 million.
Removed
Property Leases – Not Yet Commenced In February 2022, we entered into a lease agreement for office, general laboratory and planned good manufacturing practice (“GMP”) manufacturing space at 840 Winter Street in Waltham, Massachusetts, which is described in further detail in Note 12 of the consolidated financial statements included in this Annual Report on Form 10-K.
Removed
In connection therewith, we have committed to making at least $146.0 million in rental payments over a lease term of 144 months estimated to begin in the second half of 2024.
Removed
Other Obligations We enter into contracts in the normal course of business with various third parties for clinical trials, preclinical research studies, supply manufacturing and other services and products for operating purposes. These contracts are generally cancelable at any time by us upon prior written notice.
Removed
In January 2023, a research milestone related to Rewrite was achieved and settled (see Note 11 of the consolidated financial statements included in this Annual Report on Form 10-K ).
Removed
We only apply the five-step model to contracts when 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.
Removed
Significant judgments made with respect to stock-based compensation relate to certain assumptions made when selecting model inputs used in the Black-Scholes option pricing model, in particular the volatility and expected life assumptions. Volatility assumptions are calculated based on historical volatility of the Company’s stock. We estimate the expected term of options using the simplified method.
Removed
In addition, an expected dividend yield of zero is used in the option valuation model because we do not pay cash dividends and do not expect to pay any cash dividends in the foreseeable future.
Removed
Stock-based compensation expense for an award with performance conditions also include significant judgment with respect to the probability that the performance condition will be achieved, as the amount of expense recorded is based on the probable outcome of the performance conditions.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

5 edited+0 added−0 removed1 unchanged
Biggest changeFinancial Statement s and Supplementary Data The information required by this item is presented at the end of this report beginning on page F-1. Item 9. Changes in and Disagreements with Accou ntants on Accounting and Financial Disclosure None. 100
Biggest changeFinancial Statements and Supplementary Data The information required by this item is presented at the end of this report beginning on page F-1. Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure None.
Due to the short-term duration of our investment portfolios and the low risk profile of our investments, we do not believe an immediate change of 100 basis points, or one percentage point, would have a material effect on the fair market value of our investment portfolio. Declines in interest rates, however, would reduce future investment income.
Due to the short-term duration of our investment portfolios and the low risk profile of our investments, we do not believe an immediate change of 100 basis points, or one percentage point, would have a material effect on the fair market value of our investment portfolio. Declines in interest rates, however, would reduce future interest income.
We do not have any foreign currency or derivative financial instruments. Inflation generally affects us by increasing our cost of labor, preclinical and clinical trial costs. We do not believe that inflation had a material effect on our results of operations during the year ended December 31, 2023. Item 8.
We do not have any foreign currency or derivative financial instruments. Inflation generally affects us by increasing our cost of labor, preclinical and clinical trial costs. We do not believe that inflation had a material effect on our results of operations during the year ended December 31, 2024. Item 8.
Item 7A. Quantitative and Qualitati ve Disclosures about Market Risk The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates.
Item 7A. Quantitative and Qualitative Disclosures about Market Risk The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates.
As of December 31, 2023, we had cash equivalents, restricted cash equivalents and marketable securities of $921.6 million consisting of interest-bearing money market accounts, corporate and financial institution debt securities, U.S. Treasury and other government securities and asset-backed securities.
As of December 31, 2024, we had cash equivalents, restricted cash equivalents and marketable securities of $739.4 million consisting of interest-bearing money market accounts, corporate and financial institution debt securities, U.S. Treasury and other government securities and asset-backed securities.

Other NTLA 10-K year-over-year comparisons