Intellia Therapeutics (NTLA) risk factors, FY2024 10-K

Risks Related to Preclinical and Clinical Development

1. 01CRISPR/Cas9 genome editing technology has only recently been clinically validated for human therapeutic use
2. 02The approaches we are taking to discover and develop novel therapeutics using CRISPR/Cas9 systems are unproven and may never lead to marketable products
3. 03If we are unable to develop viable product candidates, achieve regulatory approval for any such product candidate or market and sell any resulting product, we may never achieve profitability
4. 04indications 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
5. 05Clinical development involves a lengthy and expensive process, with an uncertain outcome
6. 06We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of any product candidates
7. 07Negative public opinion and increased regulatory scrutiny of CRISPR/Cas9 use, genome editing or gene therapy may damage public perception of the safety of our product candidates and adversely affect our ability to conduct our business or obtain regulatory approvals for such product candidates

Risks Related to the Industry

1. 08Inconclusive results, lack of efficacy, adverse events or additional safety concerns in clinical trials that we or others conduct may impede the regulatory approval process or overall market acceptance of our product candidates
2. 09experience damage to our reputation
3. 10Even if we obtain regulatory approval of any product candidates, such candidates may not gain market acceptance among physicians, patients, hospitals, third party payors and others in the medical community
4. 11the effectiveness of our sales and marketing efforts and distribution support

Risks Related to Third Party and Licensed Intellectual Property

1. 12Our commercial success depends in part on our avoiding infringement of the valid patents and proprietary rights of third parties
2. 13to have willfully infringed a patent. Any of the foregoing assertions or results could materially harm our business, cause significant costs or delays to our plans, and/or prevent us from further developing and commercializing the affected product candidates or products, thereby causing us significant harm
3. 14We have licensed intellectual property from third parties for use in our programs, and termination or modification of any of these licenses could result in the loss of those intellectual property rights, which could harm our business
4. 15the amounts of royalties, milestones or other payments due under the license agreement
5. 16We depend, in part, on our licensors to file, prosecute, maintain, defend and enforce patents and patent applications that are material to our business
6. 17We may not be successful in obtaining or maintaining in-licensed rights to product components and processes or other technology for our product development pipeline
7. 18We may be required to pay certain milestones and royalties under our license agreements with third party licensors

Risks Related to Patents and Trademarks

1. 19We could be unsuccessful in obtaining or maintaining adequate patent protection for one or more of our products or product candidates, or asserting and defending our intellectual property rights that protect our products and technologies
2. 20whether 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
3. 21owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours
4. 22We may be subject to claims challenging the inventorship of our patents and other intellectual property
5. 23We have limited foreign intellectual property rights and may not be able to protect our intellectual property rights throughout the world
6. 24We may be involved in lawsuits to protect or enforce our patents, the patents of our licensors or our licenses, which could be expensive, time-consuming, and unsuccessful
7. 25Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court or before the USPTO or comparable foreign authority
8. 26Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements
9. 27If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected

Risks Related to Potential Disclosure of Confidential Information

1. 28Confidentiality agreements with employees and third parties may not prevent unauthorized disclosure of trade secrets and other proprietary information
2. 29We may be subject to claims that our employees, directors, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties

Risks Related to Past Financial Condition

1. 30We have never generated any revenue from product sales and our ability to generate revenue from product sales and become profitable depends significantly on our success in a number of areas
2. 31selecting commercially viable product candidates and effective delivery methods
3. 32Our operating history may make difficult the evaluation of our business’s success to date and assessment of our future viability
4. 33We have incurred net losses in each period since our inception, anticipate that we will continue to incur net losses in the future and may never achieve profitability

Risks Related to Future Financial Condition

1. 34We may need to raise substantial additional funding to fund our operations. If we fail to obtain additional financing, we may be unable to complete the development and commercialization of any product candidates
2. 35testing and clinical trials for our current or future product candidates, including additional expenses attributable to adjusting our development plans (including any supply related matters)
3. 36Raising additional capital may cause dilution to our stockholders and restrict our operations
4. 37Unfavorable national or global economic conditions or political developments could adversely affect our business, financial condition or results of operations
5. 75Future 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

Risks Related to Manufacturing and Supply

1. 38In vivo genome editing products and ex vivo engineered cell therapies based on CRISPR/Cas9 genome editing technology are novel, complex and difficult to manufacture
2. 39We could experience manufacturing problems that result in delays in the development, approval or commercialization of our product candidates or otherwise harm our business

Risks Related to Obtaining Regulatory Approval

1. 40We are currently conducting and may in the future conduct other clinical trials for our product candidates outside the U.S., and the FDA and comparable foreign regulatory authorities may not accept data from such trials
2. 41Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of product candidates in other jurisdictions
3. 42Existing regulatory policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates

Risks Related to Ongoing Regulatory Obligations

1. 43candidates, 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
2. 44injunctions or the imposition of civil or criminal penalties
3. 45Our employees, independent contractors, clinical investigators, CMOs, CROs, consultants, collaborators, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business
4. 46Failure to comply with health and data protection laws and regulations could lead to government enforcement actions (which could include civil or criminal penalties), private litigation, and/or adverse publicity and could negatively affect our operating results and business
5. 47If we, or our collaborators, clinical investigators, CMOs, CROs, consultants or vendors, fail to comply with environmental, health and safety, and laboratory animal welfare laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business
6. 48Failure to comply with labor and employment laws and regulations could subject us to legal liability and costs, including fines or penalties, as well as reputational damage that could harm our business

Risks Related to Our Reliance on Collaboration Partners

1. 49Our existing and future collaborations will be important to our business. If we are unable to maintain any of these collaborations, or if these collaborations are not successful, our business could be adversely affected
2. 50may 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
3. 51Additionally, if one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception in the business and financial communities could be adversely affected

Risks Related to Our Reliance on Other Third Parties

1. 52associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations
2. 53Public health concerns and measures taken in response by U.S. or other governments may significantly impact our CROs, clinical sites and other service and goods providers, which may affect our ability to initiate and complete preclinical studies and clinical trials

Risks Related to Data and Privacy

1. 54Our 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
2. 55comply 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
3. 56Interruptions in the availability of server systems or communications with internet or cloud-based services, or failure to maintain the security, confidentiality, accessibility or integrity of data stored on such systems, could harm our business
4. 57Social media platforms and artificial intelligence-based platforms present new risks and challenges to our business
5. 58requirements depends on legal and risk determinations that rely on novel legal provisions that have not yet been interpreted by courts or regulators, and non-compliance can lead to significant fines

Risks Related to Competition

1. 59Any advances in gene therapy, engineered cell therapies or genome editing technology made by a competitor may be used to develop therapies that could compete against any of our product candidates
2. 60Many of these competitors have substantially greater research and development capabilities and financial, scientific, technical, intellectual property, manufacturing, marketing, distribution and other resources than we do, and we may not be able to successfully compete with them

Risks Related to Commercialization

1. 61unforeseen costs and expenses, as well as legal and regulatory requirements, associated with creating and operating a sales and marketing organization

Risks Related to Employee Matters and Managing Our Workforce

1. 62Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel
2. 63Execution of our business plans and strategies requires capable personnel with specialized skills and expertise in the research, development, manufacturing and commercialization of biopharmaceutical products, and, as a result, we may encounter difficulties in hiring or retaining capable personnel in key positions

Risks Related to Healthcare

1. 64Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, if approved, which could make it difficult for us to sell any product candidates or therapies profitably
2. 65such as partners and service providers, to meet these legal requirements, which could result in additional liability for us if they do not comply
3. 66Healthcare cost control initiatives, including healthcare legislative and regulatory reform measures, may have a material adverse effect on our business and results of operations

Risks Related to Investment in Securities

1. 67An active trading market for our common stock may not be sustained
2. 68The price of our common stock historically has been volatile, which may affect the price at which you could sell any shares of our common stock
3. 69the other factors summarized and described in this Risk Factors section
4. 70If securities or industry analysts do not publish research, or publish inaccurate or unfavorable research, about our business, our stock price and trading volume could decline
5. 71Because we do not anticipate paying any cash dividends on our capital stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain

Risk Related to Ownership Generally

1. 72Our principal stockholders and management own a significant percentage of our stock and, if they choose to act together, will be able to control or exercise significant influence over matters subject to stockholder approval
2. 73We have broad discretion over the use of our cash, cash equivalents and marketable securities, and may not use them effectively, including that we may be exposed to liquidity issues and other systemic financial risks at the financial institutions holding our cash and cash equivalents
3. 74We incur significant costs as a result of operating as a public company, and our management is required to devote substantial time to compliance initiatives and corporate governance practices

Risks Related to our Charter and Bylaws

1. 76Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us difficult, limit attempts by our stockholders to replace or remove our current management and adversely affect our stock price
2. 77provide 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
3. 78Our certificate of incorporation and by-laws designate certain courts as the sole and exclusive forums for certain disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees

Risks Related to Tax Matters

1. 79Changes in tax law may adversely affect our business and financial condition
2. 80Our ability to use our net operating loss (“NOL”) carryforwards and certain other tax attributes may be limited