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What changed in Beam Therapeutics Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Beam Therapeutics Inc.'s 2024 and 2025 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 2025 report.

+636 added−581 removedSource: 10-K (2026-02-24) vs 10-K (2025-02-25)

Top changes in Beam Therapeutics Inc.'s 2025 10-K

636 paragraphs added · 581 removed · 427 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

168 edited+84 added−92 removed482 unchanged
Biggest changeOur wholly owned and our in-licensed patents and patent applications cover various aspects of our base editing platform and our programs, including: • C-to-T DNA base editors • A-to-G DNA base editors • A-to-I RNA base editors, or REPAIR • C-to-U RNA base editors, or RESCUE • Dual editing C-to-T and A-to-G DNA base editors • CRISPR/Cas12b systems for nuclease editing • Novel guide RNA sequences • Systems and methods for increasing the specificity of base editing • Multiplex base editing in immune cells ex vivo • Methods for evaluating base editing specificity • Therapeutic methods • Delivery modality We also have an option to license patents and patent applications relating to CRISPR/Cas9 systems.
Biggest changeOur wholly owned and our in-licensed patents and patent applications cover various aspects of our base editing platform and our programs, including various gene editors, guide RNA sequences, systems and methods for increasing the specificity of gene editing, therapeutic methods, and various modalities for delivery gene editors. 12 We also have an option to license patents and patent applications relating to CRISPR/Cas9 systems.
Following the signing of the Editas License Agreement, we obtained the right to further sublicense our rights the licensed patents from Broad Institute and Harvard to third parties, provided that we comply with certain sublicensing requirements under each of the Broad/Harvard Head Licenses as if we were Editas, as well as certain other customary conditions.
Following the signing of the Editas License Agreement, we obtained the right to further sublicense our rights to the licensed patents from Broad Institute and Harvard to third parties, provided that we comply with certain sublicensing requirements under each of the Broad/Harvard Head Licenses as if we were Editas, as well as certain other customary conditions.
Data Protection Act of 2018 applies to the processing of personal data that takes place in the U.K. and includes parallel obligations to those set forth by GDPR.
Data Protection Act of 2018 applies to the processing of personal data that takes place in the U.K. and includes parallel obligations to those set forth by the GDPR.
Other EU Member States allow companies to fix their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.
Other EU Member States allow companies to fix their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.
We believe our base editing platform offers meaningful advantages over established approaches in gene editing, including: • Highly precise and predictable gene editing, designed to make only one type of base edit at the desired target location; • Highly efficient and therapeutically relevant levels of gene correction, which are generally unachievable by nuclease-based editing methods; • Broad applicability in a wide range of cell types, including both dividing and non-dividing cells; • Direct chemical modification of DNA with no requirement for delivery of the corrected DNA sequence; • Avoidance of unwanted DNA modifications associated with double-stranded breaks, including gene disruptions and chromosomal rearrangements, such as translocations or deletions; • The potential for permanent editing of genes, creating the opportunity for a life-long therapeutic outcome, including the ability to treat infants or young children since the edit will be passed on by dividing cells as the child grows; • Multiple applications, including gene correction, gene silencing, gene activation, gene modification and/or multiplex editing of several genes simultaneously • Preservation of natural regulation and a normal number of copies of the gene in the cell by modification of genes in their native genomic setting; and • A versatile and modular product engine that can target a different gene sequence with the same base editor and a different guide RNA.
We believe our base editing platform offers meaningful advantages over established approaches in gene editing, including: • Highly precise and predictable gene editing, designed to make only one type of base edit at the desired target location; • Highly efficient and therapeutically relevant levels of gene correction, which are generally unachievable by nuclease-based editing methods; • Broad applicability in a wide range of cell types, including both dividing and non-dividing cells; • Direct chemical modification of DNA with no requirement for delivery of the corrected DNA sequence; • Avoidance of unwanted DNA modifications associated with double-stranded breaks, including gene disruptions and chromosomal rearrangements, such as translocations or deletions; • The potential for permanent editing of genes, creating the opportunity for a life-long therapeutic outcome, including the ability to treat infants or young children since the edit will be passed on by dividing cells as the child grows; • Multiple applications, including gene correction, gene silencing, gene activation, gene modification and/or multiplex editing of several genes simultaneously 6 • Preservation of natural regulation and a normal number of copies of the gene in the cell by modification of genes in their native genomic setting; and • A versatile and modular product engine that can target a different gene sequence with the same base editor and a different guide RNA.
Additional studies may be required after approval. • Phase 1 clinical trials are initially conducted in a limited population to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion, and pharmacodynamics in healthy humans or, on occasion, in the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, in patients, such as cancer patients. 23 • Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications and determine dose tolerance and optimal dosage.
Additional studies may be required after approval. • Phase 1 clinical trials are initially conducted in a limited population to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion, and pharmacodynamics in healthy humans or, on occasion, in the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, in patients, such as cancer patients. • Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications and determine dose tolerance and optimal dosage.
In addition, we granted Bio Palette an exclusive (even as to us and our affiliates) license under certain patent rights related to base editing and gene editing owned or controlled by us to research, make, have made, import, export, distribute, use, have used, sell, have sold or offer for sale, and otherwise exploit products in the microbiome field in Asia, subject to our right, in its sole discretion, to expand Bio Palette’s license (and the applicable royalty obligations) to the entire territory.
In addition, we granted Bio Palette an exclusive (even as to us and our affiliates) license under certain patent rights related to base editing and gene editing owned or controlled by us to research, make, have made, import, export, distribute, use, have used, sell, have sold or offer for sale, and otherwise exploit products in the microbiome field in Asia, subject to our right, in its sole discretion, to expand Bio Palette’s license (and the applicable royalty obligations) to the entire 17 territory.
While these notices did not result in civil monetary penalties, the failure to submit clinical trial information to clinicaltrials.gov is a prohibited act under the FDCA with violations subject to potential civil monetary penalties of up to $10,000 for each day the violation continues. Violations may also result in injunctions and/or criminal prosecution or disqualification from federal grants.
While these notices did not result in civil monetary penalties, the failure to submit clinical trial information to clinicaltrials.gov is a prohibited act under the FDCA with violations subject to potential civil monetary penalties of up 22 to $10,000 for each day the violation continues. Violations may also result in injunctions and/or criminal prosecution or disqualification from federal grants.
As a result, increasingly high barriers are being erected to the entry of new products. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU Member States, and parallel trade, i.e., arbitrage between low-priced and high-priced member states, can further reduce prices.
As a result, increasingly high barriers are being erected to the entry of new products. Political, economic and 43 regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU Member States, and parallel trade, i.e., arbitrage between low-priced and high-priced member states, can further reduce prices.
The PREVENT Pandemics Act, which was enacted in December 2022, clarifies that foreign drug manufacturing establishments are subject to registration and listing requirements even if a drug or biologic undergoes further manufacture, preparation, propagation, compounding, or processing at a separate establishment outside the United States prior to being imported or offered for import into the United States.
The PREVENT Pandemics Act, which was enacted in December 2022, clarifies that foreign drug manufacturing establishments are subject to registration and listing requirements even if a drug or biologic undergoes further manufacture, preparation, propagation, 24 compounding, or processing at a separate establishment outside the United States prior to being imported or offered for import into the United States.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product; • fines, warning letters or holds on post-approval clinical trials; 31 • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product recall, seizure, or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product; • fines, warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product recall, seizure, or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
Specifically, the grant of an MA in the EU for products containing viable human tissues or cells such as gene therapy medicinal products is governed by Regulation 1394/2007/EC on advanced therapy medicinal products, read in combination with Directive 2001/83/EC of the European Parliament and of the Council, commonly known as the Community code on medicinal products.
Specifically, the grant of an MA in the EU for products containing 34 viable human tissues or cells such as gene therapy medicinal products is governed by Regulation 1394/2007/EC on advanced therapy medicinal products, read in combination with Directive 2001/83/EC of the European Parliament and of the Council, commonly known as the Community code on medicinal products.
A sponsor seeking approval to market and distribute a new biologic in the United States generally must satisfactorily complete each of the following steps: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practice, or GLP, regulations; • completion of the manufacture, under cGMP conditions, of the drug substance and drug product that the sponsor intends to use in human clinical trials along with required analytical and stability testing; • design of a clinical protocol and submission to the FDA of an investigational new drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; 21 • approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled human clinical trials to establish the safety, potency, and purity of the product candidate for each proposed indication, in accordance with current Good Clinical Practices, or GCP; • preparation and submission to the FDA of a Biologics License Application, or BLA, requesting marketing of the biological product for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product and proposed labelling; • review of the BLA by an FDA advisory committee, where applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with cGMP requirements; to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, strength, quality, and purity; and, if applicable, the FDA’s current Good Tissue Practice, or cGTP, requirements for the use of human cellular and tissue products; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with GLPs and GCPs and the integrity of clinical data in support of the BLA; • payment of the application fee under the Prescription Drug User Free Act, or PDUFA, unless exempted; and • FDA review and approval of the BLA, which may be subject to additional post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and any post-approval studies required by the FDA.
A sponsor seeking approval to market and distribute a new biologic in the United States generally must satisfactorily complete each of the following steps: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practice, or GLP, regulations; • completion of the manufacture, under cGMP conditions, of the drug substance and drug product that the sponsor intends to use in human clinical trials along with required analytical and stability testing; • design of a clinical protocol and submission to the FDA of an investigational new drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled human clinical trials to establish the safety, potency, and purity of the product candidate for each proposed indication, in accordance with current Good Clinical Practices, or GCP; • preparation and submission to the FDA of a BLA requesting marketing of the biological product for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product and proposed labelling; • review of the BLA by an FDA advisory committee, where applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with cGMP requirements; to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, strength, quality, and 19 purity; and, if applicable, the FDA’s current Good Tissue Practice, or cGTP, requirements for the use of human cellular and tissue products; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with GLPs and GCPs and the integrity of clinical data in support of the BLA; • payment of the application fee under the Prescription Drug User Free Act, or PDUFA, unless exempted; and • FDA review and approval of the BLA, which may be subject to additional post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and any post-approval studies required by the FDA.
Our overall goal with these platform activities is to continue expanding our access to the technologies and teams in genetic medicine that will maximize our long-term value creation and impact on patients. 7 Our base editing portfolio We are advancing multiple programs through clinical development in parallel.
Our overall goal with these platform activities is to continue expanding our access to the technologies and teams in genetic medicine that will maximize our long-term value creation and impact on patients. Our base editing portfolio We are advancing multiple programs through clinical development in parallel.
For more information regarding the risks related to our intellectual property, please see Item 1., Business—Intellectual property—Intellectual property licenses and Item 1A., Risk factors—Risks related to our intellectual property , in this Annual Report on Form 10-K. The term of individual patents depends upon the legal term for patents in the countries in which they are granted.
For more information regarding the risks related to our intellectual property, please see Item 1., Business—Intellectual property—Intellectual property licenses and Item 1A., Risk factors—Risks related to our intellectual property , in this Annual Report on Form 10-K. 13 The term of individual patents depends upon the legal term for patents in the countries in which they are granted.
If we fail to meet any of the deadlines for the development milestones, then Harvard may, depending on the nature of the failure and the impacted milestones, either terminate the Harvard License Agreement or our licenses with respect to the applicable licensed product(s), subject to certain exceptions and opportunities for us to cure such failure.
If we fail to meet any of the deadlines for the development milestones, then Harvard may, depending on the nature of the failure and the impacted milestones, either terminate the Harvard License Agreement or our licenses with respect to the applicable licensed product(s), subject to certain exceptions and 14 opportunities for us to cure such failure.
A non-significant risk device study requires only IRB approval prior to initiation of a clinical study. After a device is placed on the market, it remains subject to significant regulatory requirements. Medical devices may be marketed only for the uses and indications for which they are cleared or approved.
A non-significant risk device study requires only IRB approval prior to initiation of a clinical study. 32 After a device is placed on the market, it remains subject to significant regulatory requirements. Medical devices may be marketed only for the uses and indications for which they are cleared or approved.
It also requires the submission to the relevant competent authorities of a marketing authorization application, or MAA, and granting of a marketing authorization by these authorities before the product can be marketed and sold in the EU. 35 Non-clinical studies Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances.
It also requires the submission to the relevant competent authorities of a marketing authorization application, or MAA, and granting of a marketing authorization by these authorities before the product can be marketed and sold in the EU. Non-clinical studies Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances.
Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the 43 negotiated “maximum fair price” under the law or for taking price increases that exceed inflation.
Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation.
The FDA may request additional information rather than accept a BLA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. 27 After the submission is accepted for filing, the FDA begins an in-depth substantive review of the application.
The FDA may request additional information rather than accept a BLA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. After the submission is accepted for filing, the FDA begins an in-depth substantive review of the application.
For example, the State of Washington passed the My Health My Data Act in 2023 which specifically regulated health information that is not otherwise regulated by the HIPAA rules, and the law also has a private right of action, which further increases the relevant compliance risk.
For 33 example, the State of Washington passed the My Health My Data Act in 2023 which specifically regulated health information that is not otherwise regulated by the HIPAA rules, and the law also has a private right of action, which further increases the relevant compliance risk.
The sublicensing party is also responsible for any breaches of such terms by the applicable sublicensee and is responsible for all payments due under the Bio Palette License Agreement by operation of any such sublicense. 20 Upon the execution of the Bio Palette License Agreement, we paid Bio Palette an upfront fee of $0.5 million.
The sublicensing party is also responsible for any breaches of such terms by the applicable sublicensee and is responsible for all payments due under the Bio Palette License Agreement by operation of any such sublicense. Upon the execution of the Bio Palette License Agreement, we paid Bio Palette an upfront fee of $0.5 million.
With passage of FDORA, Congress clarified the FDA’s authority to conduct inspections by expressly permitting inspection of facilities involved in the preparation, conduct, or analysis of clinical and non-clinical studies submitted to FDA as well as other persons holding study records or involved in the study process.
With passage of FDORA, Congress clarified the FDA’s 25 authority to conduct inspections by expressly permitting inspection of facilities involved in the preparation, conduct, or analysis of clinical and non-clinical studies submitted to FDA as well as other persons holding study records or involved in the study process.
The federal government has levied large civil and criminal fines against companies for alleged improper promotion and has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.
The federal government has levied large civil and criminal fines 29 against companies for alleged improper promotion and has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.
All of the components of the LNP, as well as the mRNA encoding the base editor, are well-defined and can be manufactured synthetically, providing the opportunity for scalable manufacturing. We are currently using LNPs to advance BEAM-302 and BEAM-301.
All of the components of the LNP, as well as the mRNA encoding the base editor, are well-defined and can be manufactured synthetically, providing the opportunity for scalable manufacturing. We are currently using LNPs to advance BEAM-302, BEAM-304 and BEAM-301.
Generally, pivotal trials are Phase 3 trials, but they may be Phase 2 trials if the design provides a well-controlled and reliable assessment of clinical benefit, particularly in an area of unmet medical need.
Generally, pivotal trials are Phase 3 trials, but 21 they may be Phase 2 trials if the design provides a well-controlled and reliable assessment of clinical benefit, particularly in an area of unmet medical need.
We believe this model will help us to unlock the full potential of precision genetic medicine across a wider array of possible applications, including many outside our core areas of focus.
We believe this model will help us to 7 unlock the full potential of precision genetic medicine across a wider array of possible applications, including many outside our core areas of focus.
The upfront fee, equity issuance, and option exercise payments we make to Editas under 17 the Editas License Agreement constitute both consideration for the licenses granted to us under the Editas License Agreement and reimbursement for prosecution and maintenance costs for the licensed patents.
The upfront fee, equity issuance, and option exercise payments we make to Editas under the Editas License Agreement constitute both consideration for the licenses granted to us under the Editas License Agreement and reimbursement for prosecution and maintenance costs for the licensed patents.
The Consolidated Appropriations Act’s health care offset title includes Section 4163, which extends the 2% Budget Control Act of 2011 Medicare sequester for six months into fiscal 2032 and lowers the payment reduction percentages in fiscal 2030 and 2031. 42 The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
The Consolidated Appropriations Act’s health care offset title includes Section 4163, which extends the 2% Budget Control Act of 2011 Medicare sequester for six months into fiscal 2032 and lowers the payment reduction percentages in fiscal 2030 and 2031. 41 The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
The patents and applications from our in-licensed portfolio for delivery technologies include claims to novel lipid-based delivery systems and compositions, viral-based delivery systems and compositions, and methods of using such systems and compositions to deliver base editors.
The patents and applications from our in-licensed portfolio for delivery technologies include claims to novel lipid-based delivery systems and compositions, and methods of using such systems and compositions to deliver base editors.
One third-party payor’s decision to cover a particular drug product or service does not ensure that other payors will also provide coverage for the drug product or will provide coverage at an adequate reimbursement rate. 40 Third-party payors are increasingly challenging the price and examining the cost-effectiveness of new products and services in addition to their safety, purity and potency.
One third-party payor’s decision to cover a particular drug product or service does not ensure that other payors will also provide coverage for the drug product or will provide coverage at an adequate reimbursement rate. 39 Third-party payors are increasingly challenging the price and examining the cost-effectiveness of new products and services in addition to their safety, purity and potency.
There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products, if approved in those countries. 41 Healthcare law and regulation Healthcare providers and third-party payors play a primary role in the recommendation and prescription of pharmaceutical products that are granted marketing approval.
There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products, if approved in those countries. 40 Healthcare law and regulation Healthcare providers and third-party payors play a primary role in the recommendation and prescription of pharmaceutical products that are granted marketing approval.
We also have approximately 26 pending patent applications between the Broad Institute, Inc., UCL Business, Ltd., and Apellis Pharmaceuticals, Inc. The patents and patent applications outside of the United States were filed in numerous jurisdictions, including Australia, Brazil, Canada, China, Europe, Hong Kong, India, Japan, Korea, Singapore and South Africa.
We also have approximately 24 pending patent applications between the Broad Institute, Inc., UCL Business, Ltd., and Apellis Pharmaceuticals, Inc. The patents and patent applications outside of the United States were filed in numerous jurisdictions, including Australia, Brazil, Canada, China, Europe, Hong Kong, India, Japan, Korea, Singapore and South Africa.
While we were not self-certified under the Privacy Shield, this CJEU decision has lead to increased scrutiny on data transfers from the EU to the U.S. generally and increase our costs of compliance with data privacy legislation as well as our costs of negotiating appropriate privacy and security agreements with our vendors and business partners.
While we were not self-certified under the Privacy Shield, this CJEU decision has led to increased scrutiny on data transfers from the EU to the U.S. generally and increase our costs of compliance with data privacy legislation as well as our costs of negotiating appropriate privacy and security agreements with our vendors and business partners.
Certain of our owned patents and patent applications are related to viral and non-viral delivery technologies. If issued as U.S. patents, and if the appropriate maintenance fees are paid, the U.S. patents would be expected to expire between 2039 and 2045, excluding any additional term for patent term adjustments or patent term extensions.
Certain of our owned patents and patent applications are related to viral and non-viral delivery technologies. If issued as U.S. patents, and if the appropriate maintenance fees are paid, the U.S. patents would be expected to expire between 2039 and 2046, excluding any additional term for patent term adjustments or patent term extensions.
GSD1a is an autosomal recessive disorder caused by mutations in the G6PC gene that disrupts a key enzyme, G6Pase, critical for maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can result in seizures and be fatal.
GSDIa is an autosomal recessive disorder caused by mutations in the G6PC gene that disrupts a key enzyme, G6Pase, critical for maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can result in seizures and be fatal.
Our current in-licensed patents and patent applications, if the appropriate maintenance fees are paid, are expected to expire between 2034 and 2040, excluding any additional term for patent term adjustments or patent term extensions (or the corresponding foreign equivalent).
Our current in-licensed patents and patent applications, if the appropriate maintenance fees are paid, are expected to expire between 2034 and 2044, excluding any additional term for patent term adjustments or patent term extensions (or the corresponding foreign equivalent).
BEAM-301: In vivo LNP liver-targeting for GSD1a BEAM-301 is a liver-targeting LNP formulation of base editing reagents designed to correct the R83C mutation, the most prevalent disease-causing mutation for, and the mutation which results in the most severe form of, GSD1a.
BEAM-301: In vivo LNP liver-targeting for GSDIa BEAM-301 is a liver-targeting LNP formulation of base editing reagents designed to correct the R83C mutation, the most prevalent disease-causing mutation for, and the mutation which results in the most severe form of, GSDIa.
The patents and applications from our in-licensed portfolio for DNA base editing include claims to novel base editors, claims to engineered deaminase enzymes (e.g., evolved TadA) used in the base editors, compositions including the base editor or engineered deaminase as a component, methods of using such base editors, including methods of using such base editors for therapeutic indications, and guide RNAs that target base editors to therapeutically relevant DNA sequences.
The patents and applications from our in-licensed portfolio for DNA base editing include claims to novel base editors, claims to engineered deaminase enzymes (e.g., compositions including the base editor or engineered deaminase as a component, methods of using such base editors, including methods of using such base editors for therapeutic indications, and guide RNAs that target base editors to therapeutically relevant DNA sequences.
The FDA may inform the sponsor of certain requirements for information when it accepts the BLA or by the 74 th day of the receipt of the BLA. Thereafter, the FDA may submit “information requests” to the sponsor in the course of the agency’s review of the BLA.
The FDA may inform the sponsor of certain requirements for information when it accepts the BLA or by the 74 th day of the receipt of the BLA. Thereafter, the FDA may submit “information requests” to the sponsor in the course of the FDA’s review of the BLA.
Under the terms of the agreement, we granted Prime Medicine a non-exclusive license to certain of its CRISPR technology (including Cas12b), delivery technology and certain other technology controlled by us to develop and commercialize gene editing products for the treatment of human diseases.
Under the terms of the agreement, we granted Prime Medicine a non-exclusive license to certain CRISPR technology, delivery technology and certain other technology controlled by us to develop and commercialize gene editing products for the treatment of human diseases.
The RRs notably include the EMA and regulators in the EEA member states for approvals in the EU centralized procedure and mutual recognition procedure, as well as the FDA for product approvals granted in the U.S. The RR assessment must have undergone a full and standalone review.
The RRs notably include the EMA and regulators in the EEA member states for approvals in the EU centralized procedure and mutual recognition procedure, as well as the FDA for product approvals granted in the United States. The RR assessment must have undergone a full and standalone review.
We are currently prioritizing the lead programs in our hematology and genetic disease portfolios, each of which have the potential to provide differentiated therapies for significant patient populations with high unmet medical need: • BEAM-101 is a patient-specific, autologous hematopoietic stem cell, or HSC, investigational therapy designed to offer a potentially best-in-class profile, incorporating base edits that are intended to alleviate the effects of sickle cell disease by increasing fetal hemoglobin, which is expected to increase functional hemoglobin production and, in the case of sickle cell disease, inhibit hemoglobin S polymerization.
We are currently prioritizing the lead programs in our hematology and genetic disease portfolios, each of which have the potential to provide differentiated therapies for significant patient populations with high unmet medical need: • Ristoglogene autogetemcel, or risto-cel (formerly known as BEAM-101), is a patient-specific, autologous hematopoietic stem cell, or HSC, investigational therapy designed to offer a potentially best-in-class profile, incorporating base edits that are intended to alleviate the effects of sickle cell disease by increasing fetal hemoglobin, which is expected to increase functional hemoglobin production and, in the case of sickle cell disease, inhibit hemoglobin S polymerization.
BEAM-101 is a patient-specific, autologous HSC investigational therapy designed to offer a potentially best-in-class profile, incorporating base edits that are intended to mimic single nucleotide polymorphisms seen in individuals with hereditary persistence of fetal hemoglobin, or HPFH.
Risto-cel is a patient-specific, autologous HSC investigational therapy designed to offer a potentially best-in-class profile, incorporating base edits that are intended to mimic single nucleotide polymorphisms seen in individuals with hereditary persistence of fetal hemoglobin, or HPFH.
Marketing authorization To obtain a marketing authorization, or MA, for a gene therapy product under the EU regulatory system, a sponsor must submit an application via the centralized procedure administered by the European Medicines Agency, or EMA.
Marketing authorization To obtain a marketing authorization, or MA, for a gene therapy product under the EU regulatory system, a sponsor must submit an application via the centralized procedure administered by the EMA.
For information related to our in-licensed intellectual property, see the subsection below titled “—Intellectual Property Licenses.” We also have a nonexclusive license to conduct research activities and an option to exclusively license certain patents and patent applications directed to Cas9 and Cas12a from Editas, who in turn has licensed such patents from various academic institutions.
For information related to our in-licensed intellectual property, see the subsection below titled “—Intellectual Property Licenses.” We also have a nonexclusive license to conduct research activities and an option to exclusively license certain patents and patent applications directed to Cas9 and Cas12a from Editas Medicine, Inc., or Editas, which in turn has licensed such patents from various academic institutions.
There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries. Human Capital Resources As of December 31, 2024, we had 483 team members employed with us full-time, of which 115 had a M.D. or Ph.D. degree.
There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries. Human Capital Resources As of December 31, 2025, we had 511 team members employed with us full-time, of which 118 had a M.D. or Ph.D. degree.
As of December 31, 2024, our registered trademark portfolio contained approximately 33 registered/allowed trademarks and pending trademark applications in the United States and in certain overseas jurisdictions. Intellectual property licenses We are a party to a number of license agreements under which we license patents, patent applications, and other intellectual property from third parties.
As of December 31, 2025, our registered trademark portfolio contained 35 registered/allowed trademarks and pending trademark applications in the United States and in certain overseas jurisdictions. Intellectual property licenses We are a party to a number of license agreements under which we license patents, patent applications, and other intellectual property from third parties.
Pediatric exclusivity If a sponsor obtains a marketing authorization in all EU member states, or a marketing authorization granted in the centralized procedure by the European Commission, and the study results for the pediatric population are included in the product information, even when negative, the medicine is then eligible for an additional six-month period of qualifying patent protection through extension of the term of the Supplementary Protection Certificate, or SPC. 38 Patent term extensions in the EU and other jurisdictions The EU also provides for patent term extension through SPCs.
Pediatric exclusivity If a sponsor obtains a marketing authorization in all EU member states, or a marketing authorization granted in the centralized procedure by the European Commission, and the study results for the pediatric population are included in the product information, even when negative, the medicine is then eligible for an additional six-month period of qualifying patent protection through extension of the term of the Supplementary Protection Certificate, or SPC.
We intend to continue to pursue, when possible, additional patent protection, including composition of matter, method of use, and process claims, directed to each component of our platform technology and the programs in our portfolio. As of December 31, 2024, our wholly-owned patent portfolio consisted of eight issued U.S. patents, and 21 issued patents in jurisdictions outside the United States.
We intend to continue to pursue, when possible, additional patent protection, including composition of matter, method of use, and process claims, directed to each component of our platform technology and the programs in our portfolio. As of December 31, 2025, our wholly-owned patent portfolio consisted of 12 issued U.S. patents, and 57 issued patents in jurisdictions outside the United States.
The submission will be made through the Clinical Trials Information System, a new clinical trials portal overseen by the EMA and available to clinical trial sponsors, competent authorities of the EU Member States and the public.
The submission will be made through the Clinical Trials Information System, a new clinical trials portal overseen by the European Medicines Agency, or the EMA, and available to clinical trial sponsors, competent authorities of the EU Member States and the public.
We are conducting a Phase 1/2 clinical trial designed to assess the safety and efficacy of BEAM-101 for the treatment of sickle cell disease, which we refer to as our BEACON trial.
We are conducting a Phase 1/2 clinical trial designed to assess the safety and efficacy of risto-cel for the treatment of sickle cell disease, which we refer to as our BEACON trial.
BEAM-101 aims to alleviate the effects of sickle cell disease by increasing HbF, which is expected to increase functional hemoglobin production and, in the case of sickle cell disease, inhibit hemoglobin S polymerization.
Risto-cel aims to alleviate the effects of sickle cell disease by increasing HbF, which is expected to increase functional hemoglobin production and, in the case of sickle cell disease, inhibit hemoglobin S polymerization.
Many of our owned patents and patent applications are related to our DNA base editing technology, including claims to base editor variants with enhanced activities or novel properties, methods of using such base editors, methods of using such base editors for therapeutic 13 indications, multiplex base editing in immune cells ex vivo , guide RNAs that target base editors to therapeutically relevant DNA sequences, and methods for evaluating base editing specificity.
Many of our owned patents and patent applications are related to our DNA base editing technology, including claims to base editor variants with enhanced activities or novel properties, methods of using such base editors, methods of using such base editors for therapeutic indications, guide RNAs that target base editors to therapeutically relevant DNA sequences, and methods for evaluating base editing specificity.
In June 2023, the FDA issued draft guidance with updated recommendations for GCPs aimed at modernizing the design and conduct of clinical trials. The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products.
In September 2025, the FDA issued final guidance with updated recommendations for GCPs aimed at modernizing the design and conduct of clinical trials. The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products.
It is estimated that approximately 100,000 individuals in the United States have two copies of the Z allele. There are currently no curative treatments for patients with AATD. We are conducting a Phase 1/2 open label, dose escalation clinical trial of BEAM-302 at sites located in the United Kingdom for the treatment of AATD.
It is estimated that approximately 100,000 individuals in the United States have two copies of the Z allele. There are currently no curative treatments for patients with AATD. We are conducting a Phase 1/2 open label, dose exploration and dose expansion clinical trial of BEAM-302 for the treatment of AATD.
Our license to Orbital is for all fields other than our exclusive field and also excludes the targets and substantially all of the indications that are the subject of our existing programs.
Our license to Orbital is for all fields other than the Beam field, as described below, and also excludes the targets and substantially all of the indications that are the subject of our existing programs.
The fee required for the submission of a BLA under the Prescription Drug User Fee Act, or PDUFA, is substantial (for example, for federal fiscal year 2025, this application fee is approximately $4.3 million), and the sponsor of an approved BLA is also subject to an annual program fee, set at $403,889 per eligible prescription drug product for federal fiscal year 2024.
The fee required for the submission of a BLA under the Prescription Drug User Fee Act, or PDUFA, is substantial (for example, for federal fiscal year 2026, this application fee is approximately $4.7 million), and the sponsor of an approved BLA is also subject to an annual program fee, set at $442,213 per eligible prescription drug product for federal fiscal year 2026.
Additionally, either party may also terminate the Bio Palette License Agreement in the event of the other party’s bankruptcy or insolvency or if the other party, its affiliates or sublicensees brings a patent challenge relating to any licensed patents (but, in the case of such a patent challenge by a sublicensee, subject to a cure period for such party to terminate its agreement with the sublicensee that has taken the applicable action).
Additionally, either party may also terminate the Bio Palette License Agreement in the event of the other party’s bankruptcy or insolvency or if the other party, its affiliates or sublicensees brings a patent challenge relating to any licensed patents (but, in the case of such a patent challenge by a sublicensee, subject to a cure period for such party to terminate its agreement with the sublicensee that has taken the applicable action). 18 Standby License Agreement with Kobe University and Bio Palette We are party to a standby license agreement, or the Standby License Agreement, with Kobe University and Bio Palette, dated February 6, 2026.
This guidance builds upon existing policy regarding the labeling of companion diagnostics. In its 2014 guidance, the FDA stated that if evidence is sufficient to conclude that the companion diagnostic is appropriate for use with a specific group of therapeutic products, the companion diagnostic’s intended use/indications for use should name the specific group of therapeutic products, rather than specific products.
In its 2014 guidance, the FDA stated that if evidence is sufficient to conclude that the companion diagnostic is appropriate for use with a specific group of therapeutic products, the companion diagnostic’s intended use/indications for use should name the specific group of therapeutic products, rather than specific products.
With respect to the sale of licensed products by us, our affiliates or our sublicensees, Harvard is entitled to receive low single digit royalties on net sales of licensed products until, on a country-by-country basis, the latest of the expiration of (i) the last to expire valid claim of a licensed patent covering the applicable licensed product, (ii) the period of exclusivity associated with such licensed product in such country or (iii) a certain number of years after the first commercial sale of such licensed product in such country.
We may additionally owe Harvard success payments of up to an additional $90.0 million. 15 With respect to the sale of licensed products by us, our affiliates or our sublicensees, Harvard is entitled to receive low single digit royalties on net sales of licensed products until, on a country-by-country basis, the latest of the expiration of (i) the last to expire valid claim of a licensed patent covering the applicable licensed product, (ii) the period of exclusivity associated with such licensed product in such country or (iii) a certain number of years after the first commercial sale of such licensed product in such country.
Pediatric exclusivity Pediatric exclusivity is another type of non-patent regulatory exclusivity in the United States. Specifically, the Best Pharmaceuticals for Children Act provides for the attachment of an additional six months of exclusivity, which is added on to the term of any remaining regulatory exclusivity at the time the pediatric exclusivity is granted.
Specifically, the Best Pharmaceuticals for Children Act provides for the attachment of an additional six months of exclusivity, which is added on to the term of any remaining regulatory exclusivity at the time the pediatric exclusivity is granted.
The trial is an open-label, multi-cohort, single-ascending dose evaluation of BEAM-301 for the treatment of GSD1a in patients with the R83C mutation. Key endpoints of the trial include safety and tolerability, time to hypoglycemia during fasting, and changes from baseline in corn starch supplementation.
The trial is an open-label, multi-cohort, single-ascending dose evaluation of BEAM-301 for the treatment of GSDIa in patients with the R83C mutation. Key endpoints of the trial include safety and tolerability, time to hypoglycemia during fasting, and changes from baseline in corn starch supplementation. Dosing is complete in the first cohort and enrollment has been initiated in the second cohort.
Expanded access may be appropriate when all of the following criteria apply: patient(s) have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; the potential patient benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or condition to be treated; and the expanded use of the investigational drug for the requested treatment will not interfere with initiation, conduct, or completion of clinical investigations that could support marketing approval of the product or otherwise compromise the potential development of the product.
Expanded access may be appropriate when all of the following criteria apply: patient(s) have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; the potential patient benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or condition to be treated; and the expanded use of the investigational drug for the requested treatment will not interfere with initiation, conduct, or completion of clinical investigations that could support marketing approval of the product or otherwise compromise the potential development of the product. 20 Under the FDCA, sponsors of one or more investigational products for the treatment of a serious disease(s) or condition(s) must make publicly available their policy for evaluating and responding to requests for expanded access for individual patients.
Regulatory exclusivity In the EU, new chemical entities approved on the basis of a complete independent data package qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity pursuant to Regulation (EC) No 726/2004, as amended, and Directive 2001/83/EC, as amended.
After these five years, the authorization may be renewed on the basis of a reevaluation of the risk-benefit balance. 35 Regulatory exclusivity In the EU, new chemical entities approved on the basis of a complete independent data package qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity pursuant to Regulation (EC) No 726/2004, as amended, and Directive 2001/83/EC, as amended.
Once reinfused, the HSCs begin repopulating a portion of the bone marrow in a process known as engraftment. The engrafted, edited HSCs give rise to progenitor cell types with the corrected gene sequences. We are deploying this ex vivo approach in our BEAM-101 and ESCAPE base editing programs.
Once reinfused, the HSCs begin repopulating a portion of the bone marrow in a process known as engraftment. The engrafted, edited HSCs give rise to progenitor cell types with the corrected gene sequences. We are deploying this ex vivo approach in our risto-cel program.
In addition, such foreign trials are subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. 25 Pediatric studies Under the Pediatric Research Equity Act of 2003, or PREA, a BLA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Pediatric studies Under the Pediatric Research Equity Act of 2003, or PREA, a BLA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
For any licensed product in our licensed field and territory that receives regulatory approval, we are required to use commercially reasonable efforts to commercialize that licensed product in the relevant country. Bio Palette is required to use commercially reasonable efforts to develop a licensed product in Japan.
Bio Palette is required to use commercially reasonable efforts to develop a licensed product in Japan. For any licensed product that receives regulatory approval, Bio Palette is required to use commercially reasonable efforts to commercialize such licensed product in the relevant country.
After this date, all clinical trials (including those which are ongoing) will become subject to the provisions of the CTR. Parties conducting certain clinical trials must, as in the United States, post clinical trial information in the EU at the EU Clinical Trials Register (https://eudract.ema.europa.eu).
As of January 31, 2026, all clinical trials (including those which are ongoing) became subject to the provisions of the CTR. Parties conducting certain clinical trials must, as in the United States, post clinical trial information in the EU at the EU Clinical Trials Register (https://eudract.ema.europa.eu).
The most common treatment-emergent adverse events were consistent with busulfan conditioning, including febrile neutropenia, stomatitis and anemia. One patient died four months after BEAM-101 infusion due to respiratory failure that was determined by the investigator to be likely related to busulfan conditioning and deemed unrelated to BEAM-101. No vaso-occlusive crises were reported post-engraftment.
The most common treatment-emergent adverse events were consistent with busulfan conditioning, including febrile neutropenia, stomatitis and decreased appetite. As previously reported, one patient died four months after risto-cel infusion due to respiratory failure that was determined by the investigator to be likely related to busulfan conditioning and deemed unrelated to risto-cel. No patients experienced any investigator-reported severe vaso-occlusive crises post-engraftment.
That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America, or PhRMA, but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS.
That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America, or PhRMA, but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS. Several states have passed laws allowing for the importation of products from Canada.
Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval.
Some countries provide that products may be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval.
As of December 2024, the FDA has issued six notices of non-compliance, thereby signaling the government’s willingness to begin enforcing these requirements against non-compliant clinical trial sponsors.
As of January 31, 2026, the FDA has issued eight notices of non-compliance, thereby signaling the government’s willingness to begin enforcing these requirements against non-compliant clinical trial sponsors.
The prices of these ten drugs will become effective January 1, 2026. On January 17, 2025, CMS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations by February 1, 2025.
On January 17, 2025, CMS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations by February 1, 2025.
Following the CJEU decision, in October 2022, President Biden signed an executive order to implement the EU-U.S. Data Privacy Framework, which would serve as a replacement to the EU-U.S. Privacy Shield. The European Commission initiated the process to adopt an adequacy decision for the EU-U.S.
Following the CJEU decision, in October 2022, President Biden signed an executive order to implement the EU-U.S. Data Privacy Framework, or DPF, which would serve as a replacement to the EU-U.S. Privacy Shield.
In October 2023, we entered into a transfer and delegation agreement, or the Lilly Agreement, with Eli Lilly and Company, or Lilly, pursuant to which Lilly acquired certain assets and other 11 rights under the Verve Agreement, including our opt-in rights to co-develop and co-commercialize each of Verve’s base editing programs for cardiovascular disease, which consist of programs targeting PCSK9, ANGPTL3 and an undisclosed liver-mediated, cardiovascular target.
In October 2023, we entered into a transfer and delegation agreement, or the Lilly Agreement, with Eli Lilly and Company, or Lilly, pursuant to which Lilly acquired certain assets and other rights under the Verve Agreement, including our opt-in rights to co-develop and co-commercialize each of Verve’s base editing programs.
The draft guidance is adopted from the International Council for Harmonisation’s, or ICH, recently updated E6(R3) draft guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise.
The final guidance is adopted from the International Council for Harmonisation’s, or ICH, recently updated E6(R3) final guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise. In addition, the FDA issued final guidance outlining recommendations for the implementation of decentralized clinical trials.
This may include other types of therapies, such as small molecule, antibody, and/or protein therapies. 12 In addition, many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, conducting preclinical studies and clinical trials and seeking approval for products than we do today.
In addition, many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, conducting preclinical studies and clinical trials and seeking approval for products than we do today.
As of December 31, 2024, our in-licensed patent portfolio consisted of approximately 64 issued U.S. patents, and approximately 265 issued patents in jurisdictions outside the United States. We also have approximately 350 pending patent applications, including PCT applications, provisional patent applications and counterparts to the foregoing U.S. and foreign patents.
As of December 31, 2025, our in-licensed patent portfolio consisted of more than 75 issued U.S. patents, and more than 150 issued patents in jurisdictions outside the United States. We also have more than 300 pending patent applications, including PCT applications, provisional patent applications and counterparts to the foregoing U.S. and foreign patents.
Research conducted at such institutions that involves the transfer of recombinant or synthetic nucleic acid molecules, or DNA or RNA derived from recombinant or synthetic nucleic acid molecules, into human subjects must undergo review and approval by an IBC before it commences.
Research conducted at such institutions that involves the transfer of recombinant or synthetic nucleic acid molecules, or DNA or RNA derived from recombinant or synthetic nucleic acid molecules, into human subjects must undergo review and approval by an IBC before it commences. Many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

176 edited+73 added−40 removed857 unchanged
Biggest changeMoreover, if any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model or our stock performance, or if our operating results fail to meet the expectations of the investor community, one or more of the analysts who cover our company may change their recommendations regarding our company, and our stock price could decline. 105 Our internal computer systems, or those of our third-party vendors, collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our product development programs, compromise sensitive information related to our business or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business.
Biggest changeOur internal computer systems, or those of our third-party vendors, collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our product development programs, compromise sensitive information related to our business or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business.
If any of the events or developments described below were to occur, our business, prospects, operating results and financial condition could suffer materially, the trading price of our common stock could decline. The risks and uncertainties described below are not the only ones we face.
If any of the events or developments described below were to occur, our business, prospects, operating results and financial condition could suffer materially, and the trading price of our common stock could decline. The risks and uncertainties described below are not the only ones we face.
In addition, if patients are unwilling to participate in our base editing trials because of negative publicity from adverse events related to the biotechnology, gene therapy, or 54 gene editing fields, competitive clinical trials for similar patient populations, clinical trials in competing products, or for other reasons, the timeline for recruiting patients, conducting studies, and obtaining regulatory approval of any product candidates we may develop may be delayed.
In addition, if patients are unwilling to participate in our base editing trials because of negative publicity from adverse events related to the biotechnology, gene therapy, or gene editing fields, competitive clinical trials for similar patient populations, clinical trials in competing products, or for other reasons, the timeline for recruiting patients, conducting studies, and obtaining regulatory approval of any product candidates we may develop 54 may be delayed.
If we license rights to any product candidates, we may develop we or our collaborators may develop, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate them with our existing operations and company culture.
If we license rights to any product candidates we or our collaborators may develop, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate them with our existing operations and company culture.
For example, we are a party to license agreements with Broad Institute, Editas, Harvard, and Bio Palette, and others, pursuant to which we in-license key patents and patent applications for our base editing platform technology and product candidates (the Broad License Agreement, the Editas License Agreement, the Harvard License Agreement and the Bio Palette License Agreement, respectively).
For example, we are a party to license agreements with Broad Institute, Editas, Harvard, and Bio Palette, and others, pursuant to which we in-license key patents and patent applications for our base editing platform technology and product candidates (the Editas License Agreement, the Harvard License Agreement and the Bio Palette License Agreement, respectively).
Although we have an option to exclusively license certain patents and patent applications directed to Cas9 and Cas12a from Editas, who in turn has licensed such patents from various academic institutions including Broad Institute, we do not currently have a license to such patents and patent applications.
Although we have an option to exclusively license certain patents and patent applications directed to Cas9 and Cas12a from Editas, who in turn has licensed such patents from various academic institutions including Broad Institute, we do not currently have a license to such patents and patent applications.
If we are unable to obtain a necessary license to a third-party patent on commercially reasonable terms, we may be unable to commercialize our base editing platform technology or product candidates or such commercialization efforts may be significantly delayed, which could in turn significantly harm our business.
If we are unable to obtain a necessary license to a third-party patent on commercially reasonable terms, we may be unable to commercialize our base editing platform technology or product candidates or such commercialization efforts may be significantly delayed, which could in turn significantly harm our business.
Patent Nos. 10,266,850; 10,227,611; 10,000,772; 10,113,167; 10,301,651; 10,308,961; 10,337,029; 10,351,878; 10,407,697; 10,358,659; 10,358,658; 10,385,360; 10,400,253; 10,421,980; 10,415,061; 10,428,352; 10,443,076; 10,487,341; 10,513,712; 10,519,467; 10,526,619; 10,533,190; 10,550,407; 10,563,227; 10,570,419; 10,577,631; 10,597,680; 10,612,045; 10,626,419; 10,640,791; 10,669,560; 10,676,759; 10,752,920; 10,774,344; 10,793,878; 78 10,900,054; 10,982,230; 10,982,231; 10,988,780; 10,988,782; 11,001,863; 11,008,589; 11,008,590; 11,028,412; 11,186,849; 11,242,543; 11,274,318; 11,293,034; 11,332,761; 11,401,532; 11,473,108; 11,479,794; 11,549,127; 11,634,730; 11,674,159; 11,814,645; 11,970,711; 12,123,015; 12,180,503; 12,180,504; 12,215,343, which are expected to expire around March 2033, excluding any additional term for patent term adjustment, or PTA, or patent term extension, or PTE, and any disclaimed term for terminal disclaimers.
Patent Nos. 10,266,850; 10,227,611; 10,000,772; 10,113,167; 10,301,651; 10,308,961; 10,337,029; 10,351,878; 10,407,697; 10,358,659; 10,358,658; 10,385,360; 10,400,253; 10,421,980; 10,415,061; 10,428,352; 10,443,076; 10,487,341; 10,513,712; 10,519,467; 10,526,619; 10,533,190; 10,550,407; 10,563,227; 10,570,419; 10,577,631; 10,597,680; 10,612,045; 10,626,419; 10,640,791; 10,669,560; 10,676,759; 10,752,920; 10,774,344; 10,793,878; 10,900,054; 10,982,230; 10,982,231; 10,988,780; 10,988,782; 11,001,863; 11,008,589; 11,008,590; 11,028,412; 11,186,849; 11,242,543; 11,274,318; 11,293,034; 11,332,761; 11,401,532; 11,473,108; 11,479,794; 11,549,127; 11,634,730; 11,674,159; 11,814,645; 11,970,711; 12,123,015; 12,180,503; 12,180,504; 12,215,343, which are expected to expire around March 2033, excluding any additional term for patent term adjustment, or PTA, or patent term extension, or PTE, and any disclaimed term for terminal disclaimers.
The market price for our common stock may be influenced by many factors, including: • the success of existing or new competitive product candidates or technologies; • the timing and results of preclinical studies and clinical trials for any product candidates that we develop; • failure or discontinuation of any of our product development and research programs; • results of preclinical studies, clinical trials, or regulatory approvals of product candidates of our competitors, or announcements about new research programs or product candidates of our competitors; • developments or changing views regarding the use of genetic medicines, including those that involve gene editing; • commencement or termination of collaborations for our product development and research programs; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents, or other proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to any of our research programs, clinical development programs, or product candidates that we may develop; • the results of our efforts to develop additional product candidates or products; • actual or anticipated changes in estimates as to financial results, development timelines, or recommendations by securities analysts; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or other stockholders; • expiration of any future market stand-off or lock-up agreements; • variations in our financial results or those of companies that are perceived to be similar to us; • changes in estimates or recommendations by securities analysts, if any, that cover our stock; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • the effects of pandemics and public health emergencies; • general economic, industry, and market conditions; and • the other factors described in this “Risk Factors” section.
The market price for our common stock may be influenced by many factors, including: • the success of existing or new competitive product candidates or technologies; • the timing and results of preclinical studies and clinical trials for any product candidates that we develop; • failure or discontinuation of any of our product development and research programs; • results of preclinical studies, clinical trials, or regulatory approvals of product candidates of our competitors, or announcements about new research programs or product candidates of our competitors; • developments or changing views regarding the use of genetic medicines, including those that involve gene editing; • commencement or termination of collaborations for our product development and research programs; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents, or other proprietary rights; 102 • the recruitment or departure of key personnel; • the level of expenses related to any of our research programs, clinical development programs, or product candidates that we may develop; • the results of our efforts to develop additional product candidates or products; • actual or anticipated changes in estimates as to financial results, development timelines, or recommendations by securities analysts; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or other stockholders; • expiration of any future market stand-off or lock-up agreements; • variations in our financial results or those of companies that are perceived to be similar to us; • changes in estimates or recommendations by securities analysts, if any, that cover our stock; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • the effects of pandemics and public health emergencies; • general economic, industry, and market conditions; and • the other factors described in this “Risk Factors” section.
Some factors from public health emergencies that could delay or otherwise adversely affect the completion of our preclinical and clinical activities and, depending on the duration of the outbreak, the initiation of any future clinical trials, as well as our business generally, include: • business disruptions caused by potential workplace, laboratory and office closures and an increased reliance on employees working from home, disruptions to or delays in ongoing laboratory experiments and operations, staffing shortages, travel limitations, cyber security and data accessibility, or communication or mass transit disruptions, any of which could adversely impact our business operations or delay necessary interactions with local regulators, ethics committees, manufacturing sites, research sites and other important agencies and contractors; • limitations on the availability of preclinical and clinical trial sites, researchers and investigators, regulatory agency personnel, and materials; • limitations on our business operations by local, state, or the federal government that could impact our ability to conduct our preclinical and clinical activities; • limitations on travel that could hinder our timelines; • interruption in global shipping affecting the transport of key materials; 104 • interruption of, or delays in receiving, key materials from our CMOs due to staffing shortages, production slowdowns or stoppages, increased demand from third parties for key materials and disruptions in delivery systems; and • disruptions to our third-party suppliers, including through the effects of facility closures, reductions in operating hours, staggered shifts and other social distancing efforts, labor shortages, decreased productivity and unavailability of materials or components.
Some factors from public health emergencies that could delay or otherwise adversely affect the completion of our preclinical and clinical activities and, depending on the duration of the outbreak, the initiation of any future clinical trials, as well as our business generally, include: • business disruptions caused by potential workplace, laboratory and office closures and an increased reliance on employees working from home, disruptions to or delays in ongoing laboratory experiments and operations, staffing shortages, travel limitations, cyber security and data accessibility, or communication or mass transit disruptions, any of which could adversely impact our business operations or delay necessary interactions with local regulators, ethics committees, manufacturing sites, research sites and other important agencies and contractors; • limitations on the availability of preclinical and clinical trial sites, researchers and investigators, regulatory agency personnel, and materials; • limitations on our business operations by local, state, or the federal government that could impact our ability to conduct our preclinical and clinical activities; • limitations on travel that could hinder our timelines; • interruption in global shipping affecting the transport of key materials; • interruption of, or delays in receiving, key materials from our CMOs due to staffing shortages, production slowdowns or stoppages, increased demand from third parties for key materials and disruptions in delivery systems; and • disruptions to our third-party suppliers, including through the effects of facility closures, reductions in operating hours, staggered shifts and other social distancing efforts, labor shortages, decreased productivity and unavailability of materials or components.
The degree of market acceptance of any product candidates we may develop, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and safety of such product candidates as demonstrated in clinical trials; • the potential and perceived advantages compared to alternative treatments; • the limitation to our targeted patient population and limitations or warnings contained in approved labeling by the FDA, EMA, or other regulatory authorities; • the ability to offer our medicines for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the clinical indications for which the product candidate is approved by the FDA, the EMA, or other regulatory agencies; • public attitudes regarding genetic medicine generally and gene editing and base editing technologies specifically; • the willingness of the target patient population to try novel therapies and of physicians to prescribe these therapies, as well as their willingness to accept a therapeutic intervention that involves the editing of the patient’s gene; • product labeling or product insert requirements of the FDA, the European Commission, the EMA, or other regulatory authorities, including any limitations or warnings contained in a product’s approved labeling; • relative convenience and ease of administration; • the timing of market introduction of competitive products; • publicity concerning our products or competing products and treatments; • the strength of marketing and distribution support; • sufficient third-party coverage or reimbursement; and • the prevalence and severity of any side effects.
The degree of market acceptance of any product candidates we may develop, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and safety of such product candidates as demonstrated in clinical trials; • the potential and perceived advantages compared to alternative treatments; 58 • the limitation to our targeted patient population and limitations or warnings contained in approved labeling by the FDA, EMA, or other regulatory authorities; • the ability to offer our medicines for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the clinical indications for which the product candidate is approved by the FDA, the EMA, or other regulatory agencies; • public attitudes regarding genetic medicine generally and gene editing and base editing technologies specifically; • the willingness of the target patient population to try novel therapies and of physicians to prescribe these therapies, as well as their willingness to accept a therapeutic intervention that involves the editing of the patient’s gene; • product labeling or product insert requirements of the FDA, the European Commission, the EMA, or other regulatory authorities, including any limitations or warnings contained in a product’s approved labeling; • relative convenience and ease of administration; • the timing of market introduction of competitive products; • publicity concerning our products or competing products and treatments; • the strength of marketing and distribution support; • sufficient third-party coverage or reimbursement; and • the prevalence and severity of any side effects.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: 76 • the scope of rights granted under the license agreement and other interpretation-related issues; • the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; • the sublicensing of patent and other rights to third parties under our collaborative development relationships; • our diligence obligations under the license agreement with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates and what activities satisfy those diligence obligations; • the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and • the priority of invention of patented technology.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; • the sublicensing of patent and other rights to third parties under our collaborative development relationships; • our diligence obligations under the license agreement with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates and what activities satisfy those diligence obligations; • the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and • the priority of invention of patented technology.
Department of Health and Human Services for re-disclosure to the public, as well as ownership and investment interests held by physicians and their immediate family members; • state laws also requiring pharmaceutical companies to comply with specific compliance standards, restrict financial interactions between pharmaceutical companies and healthcare providers or require pharmaceutical companies to report information related to payments to health care providers or marketing expenditures; and 93 • analogous state and foreign laws and regulations, such as state anti-kickback, anti-bribery and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.
Department of Health and Human Services for re-disclosure to the public, as well as ownership and investment interests held by physicians and their immediate family members; • state laws also requiring pharmaceutical companies to comply with specific compliance standards, restrict financial interactions between pharmaceutical companies and healthcare providers or require pharmaceutical companies to report information related to payments to health care providers or marketing expenditures; and • analogous state and foreign laws and regulations, such as state anti-kickback, anti-bribery and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.
Our ability to generate future revenues from product sales depends heavily on our, or our collaborators’, ability to successfully: 48 • identify product candidates and complete research and preclinical and clinical development of the product candidates we or our collaborators may identify; • seek and obtain regulatory and marketing approvals for any of our product candidates for which we or our collaborators successfully complete clinical trials; • launch and commercialize any of our product candidates for which we obtain regulatory and marketing approval by establishing a sales force, marketing, and distribution infrastructure or, alternatively, collaborating with a commercialization partner; • qualify for adequate coverage and reimbursement by government and third-party payors for our product candidates for which we or our collaborators obtain regulatory and marketing approval; • develop, maintain, and enhance a sustainable, scalable, reproducible, and transferable manufacturing process for the product candidates we or our collaborators may develop; • maintain and operate a commercial-scale cGMP manufacturing facility; • establish and maintain supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products, and services to support clinical development and the market demand for our product candidates for which we or our collaborators obtain regulatory and marketing approval; • obtain market acceptance of any product candidates we or our collaborators may develop as viable treatment options; • address competing technological and market developments; • implement internal systems and infrastructure, as needed; • negotiate favorable terms in any collaboration, licensing, or other arrangements into which we may enter and performing our obligations in such collaborations, licensing or other arrangements; • maintain, protect, enforce, defend, and expand our portfolio of intellectual property rights, including patents, trade secrets, and know-how; • avoid and defend against third-party interference, infringement, and other intellectual property claims; and • attract, hire, and retain qualified personnel.
Our ability to generate future revenues from product sales depends heavily on our, or our collaborators’, ability to successfully: 47 • identify product candidates and complete research and preclinical and clinical development of the product candidates we or our collaborators may identify; • seek and obtain regulatory and marketing approvals for any of our product candidates for which we or our collaborators successfully complete clinical trials; • launch and commercialize any of our product candidates for which we obtain regulatory and marketing approval by establishing a sales force, marketing, and distribution infrastructure or, alternatively, collaborating with a commercialization partner; • qualify for adequate coverage and reimbursement by government and third-party payors for our product candidates for which we or our collaborators obtain regulatory and marketing approval; • develop, maintain, and enhance a sustainable, scalable, reproducible, and transferable manufacturing process for the product candidates we or our collaborators may develop; • maintain and operate a commercial-scale cGMP manufacturing facility; • establish and maintain supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products, and services to support clinical development and the market demand for our product candidates for which we or our collaborators obtain regulatory and marketing approval; • obtain market acceptance of any product candidates we or our collaborators may develop as viable treatment options; • address competing technological and market developments; • implement internal systems and infrastructure, as needed; • negotiate favorable terms in any collaboration, licensing, or other arrangements into which we may enter and performing our obligations in such collaborations, licensing or other arrangements; • maintain, protect, enforce, defend, and expand our portfolio of intellectual property rights, including patents, trade secrets, and know-how; • avoid and defend against third-party interference, infringement, and other intellectual property claims; and • attract, hire, and retain qualified personnel.
Even after we receive and incorporate guidance from these regulatory authorities, the FDA, European national competent authority, or other regulatory authorities could disagree that we have satisfied their requirements to commence our clinical trial or change their position on the acceptability of our data, trial design or the clinical endpoints selected, which may require us to complete additional preclinical studies or clinical trials or impose stricter requirements for approval than we currently expect.
Even after we receive and incorporate guidance from these regulatory authorities, the FDA, European national competent authority, or other regulatory authorities could disagree that we have satisfied their requirements to commence our clinical trial or change their 50 position on the acceptability of our data, trial design or the clinical endpoints selected, which may require us to complete additional preclinical studies or clinical trials or impose stricter requirements for approval than we currently expect.
To comply with the requirements of being a public company, we have undertaken certain actions, such as documenting, reviewing and improving our internal controls and procedures for compliance with Section 404 of the Sarbanes-Oxley Act of 2002, or SOX, which requires annual management assessment of the effectiveness of our internal control over financial reporting and an annual report on and attestation to such 102 assessment by our registered public accounting firm.
To comply with the requirements of being a public company, we have undertaken certain actions, such as documenting, reviewing and improving our internal controls and procedures for compliance with Section 404 of the Sarbanes-Oxley Act of 2002, or SOX, which requires annual management assessment of the effectiveness of our internal control over financial reporting and an annual report on and attestation to such assessment by our registered public accounting firm.
In addition, in order for the FDA to grant orphan drug exclusivity to one of our product candidates, the agency must find that the product candidate is indicated for the treatment of a condition or disease that affects fewer than 200,000 individuals in the United States or that affects more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making the product candidate available for the disease or condition will be recovered from sales of the product in the United States.
In addition, in order for the FDA to grant orphan drug exclusivity to one of our product candidates, the FDA must find that the product candidate is indicated for the treatment of a condition or disease that affects fewer than 200,000 individuals in the United States or that affects more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making the product candidate available for the disease or condition will be recovered from sales of the product in the United States.
This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices. We do not expect to pay any dividends for the foreseeable future. Investors may never obtain a return on their investment unless they sell our common stock for a price higher than which they paid for it.
This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices. 103 We do not expect to pay any dividends for the foreseeable future. Investors may never obtain a return on their investment unless they sell our common stock for a price higher than which they paid for it.
Failure to comply with any of these laws and regulations could result in enforcement action against us, including fines, imprisonment of company officials and public censure, claims for damages by affected individuals, damage to our reputation and loss of goodwill, any of which could have a material adverse effect on our business, financial condition, results of operations or prospects.
Failure to comply with any of these laws and regulations could result in enforcement action against us, including fines, imprisonment 98 of company officials and public censure, claims for damages by affected individuals, damage to our reputation and loss of goodwill, any of which could have a material adverse effect on our business, financial condition, results of operations or prospects.
Our competitors or other third parties may be able to circumvent our patents by developing similar or alternative technologies or products in a non-infringing manner. 70 In addition, 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.
Our competitors or other third parties may be able to circumvent our patents by developing similar or alternative technologies or products in a non-infringing manner. In addition, 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.
Additionally, there are increased rules and regulations governing the use and development of artificial intelligence at the state, federal, and international levels, which creates potential compliance and enforcement risk. These developments could damage our reputation, result in the loss of valuable property and information, and adversely impact our business. Item 1B. Unresolve d Staff Comments. None. 106
Additionally, there are increased rules and regulations governing the use and development of artificial intelligence at the state, federal, and international levels, which creates potential compliance and enforcement risk. These developments could damage our reputation, result in the loss of valuable property and information, and adversely impact our business. Item 1B. Unresolve d Staff Comments. None.
Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely affect our business, financial condition, results of operations and growth prospects. 83 Intellectual property rights do not necessarily address all potential threats.
Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely affect our business, financial condition, results of operations and growth prospects. Intellectual property rights do not necessarily address all potential threats.
Our fourth amended certificate of incorporation, or our certificate of incorporate, and our second amended and restated by-laws, or our by-laws, and Delaware law contain provisions that may have the effect of discouraging, delaying or preventing a change in control of us or changes in our management that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares.
Our fourth amended certificate of incorporation, or our certificate of incorporation, and our second amended and restated by-laws, or our by-laws, and Delaware law contain provisions that may have the effect of discouraging, delaying or preventing a change in control of us or changes in our management that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares.
For example, the U.S. government could have certain rights in such in-licensed patents, including a non-exclusive license authorizing the U.S. government to use the invention or to have others use the invention on its behalf. If the U.S. government decides to exercise these rights, it is not required to engage us as its contractor in connection with doing so.
For example, the U.S. government could have certain rights in such in-licensed patents, including a non-exclusive license authorizing the U.S. government to use the invention or to have others use the invention on its behalf. If the U.S. government decides to exercise these rights, it is not required to engage us as its 71 contractor in connection with doing so.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average review times at the agency have fluctuated in recent years as a result.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average review times at the FDA have fluctuated in recent years as a result.
While there had been some questions about the Trump Administration’s position on this program, CMS issued a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to bring greater transparency in the negotiation program.
While there had been some questions about the Trump Administration’s position on this program, CMS issued a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new 95 administration and CMS is committed to considering opportunities to bring greater transparency in the negotiation program.
This is increasingly true with respect to products approved pursuant to the accelerated 96 approval pathway. State Medicaid programs and other payers are developing strategies and implementing significant coverage barriers, or refusing to cover these products outright, arguing that accelerated approval drugs have insufficient or limited evidence despite meeting the FDA’s standards for accelerated approval.
This is increasingly true with respect to products approved pursuant to the accelerated approval pathway. State Medicaid programs and other payers are developing strategies and implementing significant coverage barriers, or refusing to cover these products outright, arguing that accelerated approval drugs have insufficient or limited evidence despite meeting the FDA’s standards for accelerated approval.
Many foreign 57 regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the U.S. or the applicable jurisdiction.
Many foreign regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the U.S. or the applicable jurisdiction.
If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which could be costly and time-consuming, and which may result in current or future product candidates that we may develop not receiving approval for commercialization in the applicable jurisdiction.
If the FDA or any 57 comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which could be costly and time-consuming, and which may result in current or future product candidates that we may develop not receiving approval for commercialization in the applicable jurisdiction.
In the declared interference, the Boston Licensing Parties have been designated as the junior party and Toolgen has been designated as the senior party. On September 28, 2022, the PTAB issued an order suspending proceedings in the priority phase of the interference. We cannot predict with any certainty when a decision will be made.
In the declared interference, the Boston Licensing Parties have 74 been designated as the junior party and Toolgen has been designated as the senior party. On September 28, 2022, the PTAB issued an order suspending proceedings in the priority phase of the interference. We cannot predict with any certainty when a decision will be made.
Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation. These types of mechanisms include re-examination, post-grant review, inter partes review, interference proceedings, derivation proceedings, and equivalent proceedings in foreign jurisdictions (e.g., opposition proceedings).
Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation. These types of mechanisms include re-examination, post-grant review, inter partes review, interference proceedings, derivation proceedings, and 79 equivalent proceedings in foreign jurisdictions (e.g., opposition proceedings).
However, the America Invents Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents. 81 In addition, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations.
However, the America Invents Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents. In addition, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations.
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. If we do not obtain PTE and data exclusivity for any product candidates we may develop, our business may be materially harmed.
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. 81 If we do not obtain PTE and data exclusivity for any product candidates we may develop, our business may be materially harmed.
Misconduct by these parties could include intentional failures to comply with FDA regulations or the regulations applicable in the EU and other jurisdictions, provide accurate information to the FDA, the EMA, and other regulatory authorities, comply with healthcare fraud and abuse laws and regulations in the United States and abroad, report financial information or data accurately, or disclose unauthorized activities to us.
Misconduct by these parties could include intentional failures to comply with FDA regulations or the regulations applicable in the EU and other jurisdictions, provide accurate information to the FDA, the EMA, and other regulatory 96 authorities, comply with healthcare fraud and abuse laws and regulations in the United States and abroad, report financial information or data accurately, or disclose unauthorized activities to us.
Our future capital requirements will depend on many factors, including: • the cost of continuing to build our base editing platform; • the costs of acquiring licenses for the delivery modalities that will be used with our product candidates; • the scope, progress, results, and costs of discovery, preclinical development, laboratory testing, manufacturing, and clinical trials for the product candidates we may develop; • the costs of preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights, and defending intellectual property-related claims; • the costs, timing, and outcome of regulatory review of the product candidates we may develop; • the costs of preparing for and undertaking future activities, including product sales, medical affairs, marketing, manufacturing, distribution, coverage and reimbursement for any product candidates for which we receive regulatory approval to commercialize; • the success of our license agreements and our collaborations; • our ability to establish and maintain additional license agreements and collaborations on favorable terms, if at all; • the achievement of milestones or occurrence of other developments that trigger payments under any additional license agreements or collaboration agreements we obtain; • the payment of success liabilities to Harvard and Broad Institute pursuant to the respective terms of the Harvard License Agreement and the Broad Institute License Agreement, should we choose to pay in cash; • the extent to which our contingent liabilities require cash expenditures; • the extent to which we acquire or in-license products, intellectual property and technologies; • the costs of operating and expanding our manufacturing capacity; and • the costs of establishing a sales, marketing, and distribution infrastructure to commercialize any product candidates for which we may obtain marketing approval.
Our future capital requirements will depend on many factors, including: • the cost of continuing to build our base editing platform; • the costs of acquiring licenses for the delivery modalities that will be used with our product candidates; • the scope, progress, results, and costs of discovery, preclinical development, laboratory testing, manufacturing, and clinical trials for the product candidates we may develop; • the costs of preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights, and defending intellectual property-related claims; • the costs, timing, and outcome of regulatory review of the product candidates we may develop; • the costs of preparing for and undertaking future activities, including product sales, medical affairs, marketing, manufacturing, distribution, coverage and reimbursement for any product candidates for which we receive regulatory approval to commercialize; • the success of our license agreements and our collaborations; • our ability to establish and maintain additional license agreements and collaborations on favorable terms, if at all; • the achievement of milestones or occurrence of other developments that trigger payments under any additional license agreements or collaboration agreements we obtain; • the payment of success liabilities to Harvard and Broad Institute, should we choose to pay in cash; • the extent to which our contingent liabilities require cash expenditures; • the extent to which we acquire or in-license products, intellectual property and technologies; • the costs of operating and expanding our manufacturing capacity; and • the costs of establishing a sales, marketing, and distribution infrastructure to commercialize any product candidates for which we may obtain marketing approval.
Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects. 72 Our owned and in-licensed patents and patent applications may not provide sufficient protection of our platform technologies, our product candidates and our future product candidates or result in any competitive advantage.
Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects. Our owned and in-licensed patents and patent applications may not provide sufficient protection of our platform technologies, our product candidates and our future product candidates or result in any competitive advantage.
Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. Third parties have asserted and may in the future assert that we, our employees, consultants, or advisors have wrongfully used or disclosed confidential information or misappropriated trade secrets.
Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. 82 Third parties have asserted and may in the future assert that we, our employees, consultants, or advisors have wrongfully used or disclosed confidential information or misappropriated trade secrets.
Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026. The IRA further delayed implementation of this rule to January 1, 2032. 95 On August 16, 2022, the IRA was signed into law by President Biden.
Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026. The IRA further delayed implementation of this rule to January 1, 2032. On August 16, 2022, the IRA was signed into law by President Biden.
The patent prosecution process is expensive, time-consuming, and complex, and we may not be able to file, prosecute, maintain, enforce, or license all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, we may not pursue or obtain patent protection in all relevant markets.
The patent prosecution process is expensive, time-consuming, and complex, and we may not be able to file, prosecute, maintain, enforce, or license all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, we may not 69 pursue or obtain patent protection in all relevant markets.
In addition, we may need the cooperation of any such co-owners of our patents in order to enforce such patents against third parties, and such cooperation may not be provided to us. 77 Additionally, we may collaborate with academic institutions to accelerate our preclinical research or development under written agreements with these institutions.
In addition, we may need the cooperation of any such co-owners of our patents in order to enforce such patents against third parties, and such cooperation may not be provided to us. Additionally, we may collaborate with academic institutions to accelerate our preclinical research or development under written agreements with these institutions.
Furthermore, our by-laws also provide that unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States shall be the exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act.
Furthermore, our by-laws also provide that unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States shall be the exclusive forum for the resolution of 104 any complaint asserting a cause of action arising under the Securities Act.
Fast track, breakthrough, and/or RMAT designation alone do not guarantee qualification for the FDA’s priority review procedures. 90 Priority review designation by the FDA may not lead to a faster regulatory review or approval process and, in any event, does not assure FDA approval of any product candidates we may develop.
Fast track, breakthrough, and/or RMAT designation alone do not guarantee qualification for the FDA’s priority review procedures. Priority review designation by the FDA may not lead to a faster regulatory review or approval process and, in any event, does not assure FDA approval of any product candidates we may develop.
The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order, or use of medicinal products is prohibited in the EU. The provision of benefits or advantages to physicians is also governed by the national anti-bribery laws of EU Member States, such as the U.K. Bribery Act 2010.
The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order, or use of medicinal products is prohibited in the EU. The provision of benefits or advantages to physicians is 93 also governed by the national anti-bribery laws of EU Member States, such as the U.K. Bribery Act 2010.
Any of the above could have a material adverse effect on our business, financial condition, results of operations or prospects. Artificial intelligence presents risks and challenges that can impact our business including by posing security risks to our confidential information, proprietary information, and personal data.
Any of the above could have a material adverse effect on our business, financial condition, results of operations or prospects. 106 Artificial intelligence presents risks and challenges that can impact our business including by posing security risks to our confidential information, proprietary information, and personal data.
It is also possible that a third party could be granted limited licenses to some of the same technology, in certain circumstances. We may not be successful in acquiring or in-licensing necessary rights to key technologies or any product candidates we may develop.
It is also possible that a third party could be granted limited licenses to some of the same technology, in certain circumstances. 76 We may not be successful in acquiring or in-licensing necessary rights to key technologies or any product candidates we may develop.
Orphan drug exclusivity may also be lost if the FDA or EMA determines that the 92 request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of the patients with the rare disease or condition.
Orphan drug exclusivity may also be lost if the FDA or EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of the patients with the rare disease or condition.
Failure to comply with laws regarding data protection would expose us to risk of enforcement actions taken by data protection authorities in the EEA and elsewhere and carries with it the potential for significant penalties if we are found to be non-compliant.
Failure to comply with laws regarding data protection would expose us to risk of enforcement actions taken 100 by data protection authorities in the EEA and elsewhere and carries with it the potential for significant penalties if we are found to be non-compliant.
Were a noncompliance event to occur, our competitors might be able to enter the market with similar or identical products or technology, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
Were a noncompliance event to occur, our competitors might be able to 80 enter the market with similar or identical products or technology, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
If the FDA determines that a product candidate is intended to treat a serious disease or condition and, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of such disease or condition, the FDA may designate the product candidate for priority review.
If the FDA determines that a product candidate is intended to treat a serious disease or condition and, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of such disease or condition, the FDA 90 may designate the product candidate for priority review.
Even if we were able to obtain a license, it could be nonexclusive, thereby giving our competitors and other third parties access to the same technologies licensed to us, and it could require us to make substantial licensing and royalty payments.
Even if we were able to obtain a license, it could be nonexclusive, thereby giving our competitors and other 78 third parties access to the same technologies licensed to us, and it could require us to make substantial licensing and royalty payments.
Violation of the FDCA and other statutes, including the False Claims Act, relating to the promotion and advertising of prescription drugs may lead to investigations or allegations of violations of federal and state health care fraud and abuse laws and state consumer protection laws.
Violation of the FDCA and other statutes, including the False Claims Act, relating to the 89 promotion and advertising of prescription drugs may lead to investigations or allegations of violations of federal and state health care fraud and abuse laws and state consumer protection laws.
Moreover, the initiation of proceedings by third parties to challenge the scope or validity of our patent rights in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business.
Moreover, the initiation of proceedings by third parties to challenge the scope or validity of our patent rights in foreign jurisdictions could result in substantial cost and divert our efforts and attention 75 from other aspects of our business.
Even if any product candidates we may develop receive marketing approval, they may nonetheless fail to gain sufficient market acceptance by physicians, patients, healthcare payors, and others in the medical 58 community.
Even if any product candidates we may develop receive marketing approval, they may nonetheless fail to gain sufficient market acceptance by physicians, patients, healthcare payors, and others in the medical community.
These decisions could introduce 87 additional uncertainty into the regulatory process and may result in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and CMS, that we rely on.
These decisions could introduce additional uncertainty into the regulatory process and may result in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and CMS, that we rely on.
Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application.
Changes in marketing approval policies during the development period, changes in or the enactment of additional 86 statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application.
For example, in October 2023, we announced a portfolio reprioritization and strategic restructuring, including cost-reduction initiatives which resulted in the pausing or elimination of certain pipeline programs. 47 Our current and any future license agreements and collaboration agreements may also be terminated if we are unable to meet the payment or other obligations under the agreements.
For example, in October 2023, we announced a portfolio reprioritization and strategic restructuring, including cost-reduction initiatives which resulted in the pausing or elimination of certain pipeline programs. 46 Our current and any future license agreements and collaboration agreements may also be terminated if we are unable to meet the payment or other obligations under the agreements.
Our ability to commercialize any medicines successfully also will depend in part on the extent to which reimbursement for these medicines and related treatments will be available from government authorities or healthcare program, private health plans, and other organizations. Government authorities and third-party payors, such as private health plans, decide which medications they will pay for and establish reimbursement levels.
Our ability to commercialize any medicines successfully also will depend in part on the extent to which reimbursement for these medicines and related treatments will be available from government authorities or healthcare programs, private health plans, and other organizations. Government authorities and third-party payors, such as private health plans, decide which medications they will pay for and establish reimbursement levels.
Our failure to become and remain profitable would decrease the value of our company and could impair our ability to raise capital, maintain our research and development efforts, expand our business or continue our operations. 49 Our future ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.
Our failure to become and remain profitable would decrease the value of our company and could impair our ability to raise capital, maintain our research and development efforts, expand our business or continue our operations. 48 Our future ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.
There can be no assurance that the U.S. interference will be 74 resolved in favor of the Boston Licensing Parties on appeal.
There can be no assurance that the U.S. interference will be resolved in favor of the Boston Licensing Parties on appeal.
We have not yet demonstrated an ability to successfully complete any clinical trials, including large-scale, pivotal clinical trials, obtain marketing approvals, manufacture a commercial-scale medicine, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful commercialization.
We have not yet demonstrated an ability to successfully complete any pivotal clinical trials, obtain marketing approvals, manufacture a commercial-scale medicine, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful commercialization.
We completed a Section 382 study as of December 31, 2024, and determined that no historical ownership changes occurred since December 2021. In addition, we may have experienced additional ownership changes since December 31, 2024 and may experience ownership changes in the future as a result of shifts in our stock ownership, some of which are outside of our control.
We completed a Section 382 study as of December 31, 2024, and determined that no historical ownership changes occurred since December 2021. However, we may have experienced ownership changes since December 31, 2024 and may experience additional ownership changes in the future as a result of shifts in our stock ownership, some of which are outside of our control.
Our failure to become and remain profitable would decrease the value of our company and could impair our ability to raise capital, maintain our research and development efforts, expand our business, or continue our operations. 46 We will need substantial additional funding.
Our failure to become and remain profitable would decrease the value of our company and could impair our ability to raise capital, maintain our research and development efforts, expand our business, or continue our operations. 45 We will need substantial additional funding.
For example: • any product candidates we may develop will eventually become commercially available in generic or biosimilar product forms; • others may be able to make gene therapy products that are similar to any product candidates we may develop or utilize similar base editing technology but that are not covered by the claims of the patents that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • we, or our license partners or current or future collaborators, may fail to meet our obligations to the U.S. government regarding any in-licensed patents and patent applications funded by U.S. government grants, leading to the loss or unenforceability of patent rights; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; • it is possible that our pending, owned or licensed patent applications or those that we may own in the future will not lead to issued patents; • it is possible that there are prior public disclosures that could invalidate our owned or in-licensed patents, or parts of our owned or in-licensed patents; • it is possible that there are unpublished applications or patent applications maintained in secrecy that may later issue with claims covering our product candidates or technology similar to ours; • it is possible that our owned or in-licensed patents or patent applications omit individual(s) that should be listed as inventor(s) or include individual(s) that should not be listed as inventor(s), which may cause these patents or patents issuing from these patent applications to be held invalid or unenforceable; • • issued patents that we hold rights to may be held invalid, unenforceable, or narrowed in scope, including as a result of legal challenges by our competitors; • the claims of our owned or in-licensed issued patents or patent applications, if and when issued, may not cover our product candidates; • the laws of foreign countries may not protect our proprietary rights or the proprietary rights of license partners or current or future collaborators to the same extent as the laws of the United States; • the inventors of our owned or in-licensed patents or patent applications may become involved with competitors, develop products or processes that design around our patents, or become hostile to us or the patents or patent applications on which they are named as inventors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we have engaged in scientific collaborations in the past and will continue to do so in the future and our collaborators may develop adjacent or competing products that are outside the scope of our patents; • we may not develop additional proprietary technologies that are patentable; • any product candidates we develop may be covered by third parties’ patents or other exclusive rights; • the patents of others may harm our business; or • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property. 84 Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations, and prospects.
For example: • any product candidates we may develop will eventually become commercially available in generic or biosimilar product forms; • others may be able to make gene therapy products that are similar to any product candidates we may develop or utilize similar base editing technology but that are not covered by the claims of the patents that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • we, or our license partners or current or future collaborators, may fail to meet our obligations to the U.S. government regarding any in-licensed patents and patent applications funded by U.S. government grants, leading to the loss or unenforceability of patent rights; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; 83 • it is possible that our pending, owned or licensed patent applications or those that we may own in the future will not lead to issued patents; • it is possible that there are prior public disclosures that could invalidate our owned or in-licensed patents, or parts of our owned or in-licensed patents; • it is possible that there are unpublished applications or patent applications maintained in secrecy that may later issue with claims covering our product candidates or technology similar to ours; • it is possible that our owned or in-licensed patents or patent applications omit individual(s) that should be listed as inventor(s) or include individual(s) that should not be listed as inventor(s), which may cause these patents or patents issuing from these patent applications to be held invalid or unenforceable; • • issued patents that we hold rights to may be held invalid, unenforceable, or narrowed in scope, including as a result of legal challenges by our competitors; • the claims of our owned or in-licensed issued patents or patent applications, if and when issued, may not cover our product candidates; • the laws of foreign countries may not protect our proprietary rights or the proprietary rights of license partners or current or future collaborators to the same extent as the laws of the United States; • the inventors of our owned or in-licensed patents or patent applications may become involved with competitors, develop products or processes that design around our patents, or become hostile to us or the patents or patent applications on which they are named as inventors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we have engaged in scientific collaborations in the past and will continue to do so in the future and our collaborators may develop adjacent or competing products that are outside the scope of our patents; • we may not develop additional proprietary technologies that are patentable; • any product candidates we develop may be covered by third parties’ patents or other exclusive rights; • the patents of others may harm our business; or • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
The prices of these ten drugs will become effective January 1, 2026. On January 17, 2025, CMS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations by February 1, 2025.
The prices of these ten drugs became effective January 1, 2026. On January 17, 2025, CMS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations by February 1, 2025.
While the investigator determined that the patient’s death was likely related to busulfan conditioning and deemed the event unrelated to BEAM-101, we cannot be certain of these conclusions, nor that other patients will not experience adverse events from the trial’s conditioning regimen or otherwise.
While the investigator determined that the patient’s death was likely related to busulfan conditioning and deemed the event unrelated to risto-cel, we cannot be certain of these conclusions, nor that other patients will not experience adverse events from the trial’s conditioning regimen or otherwise.
Our certificate of incorporation and by-laws include provisions that: • authorize “blank check” preferred stock, which could be issued by our board of directors without stockholder approval and may contain voting, liquidation, dividend and other rights superior to our common stock; • create a classified board of directors whose members serve staggered three-year terms; • specify that special meetings of our stockholders can be called only by our board of directors; • prohibit stockholder action by written consent; • establish an advance notice procedure for stockholder approvals to be brought before an annual meeting of our stockholders, including proposed nominations of persons for election to our board of directors; • provide that vacancies on our board of directors may be filled only by a majority of directors then in office, even though less than a quorum; • provide that our directors may be removed only for cause; • specify that no stockholder is permitted to cumulate votes at any election of directors; • expressly authorized our board of directors to make, alter, amend or repeal our by-laws; and • require supermajority votes of the holders of our common stock to amend specified provisions of our certificate of incorporation and by-laws. 103 These provisions, alone or together, could delay or prevent hostile takeovers and changes in control or changes in our management.
Our certificate of incorporation and by-laws include provisions that: • authorize “blank check” preferred stock, which could be issued by our board of directors without stockholder approval and may contain voting, liquidation, dividend and other rights superior to our common stock; • create a classified board of directors whose members serve staggered three-year terms; • specify that special meetings of our stockholders can be called only by our board of directors; • prohibit stockholder action by written consent; • establish an advance notice procedure for stockholder approvals to be brought before an annual meeting of our stockholders, including proposed nominations of persons for election to our board of directors; • provide that vacancies on our board of directors may be filled only by a majority of directors then in office, even though less than a quorum; • provide that our directors may be removed only for cause; • specify that no stockholder is permitted to cumulate votes at any election of directors; • expressly authorize our board of directors to make, alter, amend or repeal our by-laws; and • require supermajority votes of the holders of our common stock to amend specified provisions of our certificate of incorporation and by-laws.
Such third party may then have full rights that are the subject of the Broad License Agreement or the Harvard License Agreement (as applicable), which could impact our competitive position and enable a third party to commercialize products similar to our potential future product candidates and technology.
Such third party may then have full rights that are the subject of the Harvard License Agreement, which could impact our competitive position and enable a third party to commercialize products similar to our potential future product candidates and technology.
If this patent is maintained by the Opposition Division with claims similar to those that were opposed, our ability to commercialize our product candidates may be adversely affected if we do not obtain a license to these patents. We may not be able to obtain any required license on commercially reasonable terms or at all.
If this patent is maintained by the Boards of Appeal with claims similar to those that were opposed, our ability to commercialize our product candidates may be adversely affected if we do not obtain a license to these patents. We may not be able to obtain any required license on commercially reasonable terms or at all.
There is also uncertainty as to how other measures being implemented by the Trump Administration across the government will impact our activities and those of the FDA and its operations. For example, the potential loss of FDA personnel could lead to further disruptions and delays in FDA review of our product candidates.
There also continues to be uncertainty as to how other measures being implemented by the current administration across the government will impact our activities and those of the FDA and its operations. For example, the potential loss of FDA personnel could lead to further disruptions and delays in FDA review of our product candidates.
Since inception, we have incurred significant operating losses. Our net loss was $376.7 million, $132.5 million and $289.1 million for the years ended December 31, 2024, 2023 and 2022, respectively. As of December 31, 2024, we had an accumulated deficit of $1.6 billion.
Since inception, we have incurred significant operating losses. Our net loss was $80.0 million, $376.7 million and $132.5 million for the years ended December 31, 2025, 2024 and 2023, respectively. As of December 31, 2025, we had an accumulated deficit of $1.6 billion.
In addition to side effects and adverse events caused by our product candidates, the conditioning administration process or related procedures used in BEAM-101 and potentially other ex vivo product candidates also can cause adverse side effects and adverse events.
In addition to side effects and adverse events caused by our product candidates, the conditioning administration process or related procedures used in risto-cel and potentially other ex vivo product candidates also can cause adverse side effects and adverse events.
Some of these competitive products and therapies are based on scientific approaches that are the same as or similar to our approach, and others are based on entirely different approaches. There are several other companies utilizing base editing technology, including PerkinElmer, Life Edit (an ElevateBio company), Metagenomi, Revvity and Intellia Therapeutics.
Some of these competitive products and therapies are based on scientific approaches that are the same as or similar to our approach, and others are based on entirely different approaches. There are several other companies utilizing base editing technology, including Life Edit (an ElevateBio company), Metagenomi, Revvity, Aurora Therapeutics, Mammoth Biosciences, YolTech Therapeutics, HuidaGene Therapeutics and Intellia Therapeutics.
For example, a patient in our BEACON trial for the treatment of sickle cell disease died due to respiratory failure four months after busulfan conditioning and infusion with BEAM-101.
For example, a patient in our BEACON trial for the treatment of sickle cell disease died due to respiratory failure four months after busulfan conditioning and infusion with risto-cel.
While we may seek fast track, breakthrough, and/or RMAT designation, there is no guarantee that we will be successful in obtaining any such designation. Even if we do obtain such designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures.
While we have in the past sought, and may again in the future seek, fast track, breakthrough, and/or RMAT designation, there is no guarantee that we will be successful in obtaining any such designation. Even if we do obtain such designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures.
We anticipate that our expenses will increase substantially if and as we: • advance clinical trials of our product candidates; • continue our research programs and our preclinical development of other product candidates from our research programs; • seek to identify additional research programs and additional product candidates; • initiate preclinical testing and clinical trials for any other product candidates we identify and develop; • maintain, expand, enforce, defend and protect our intellectual property portfolio and provide reimbursement of third-party expenses related to our patent portfolio; • seek marketing approvals for any of our product candidates that successfully complete clinical trials; • establish a sales, marketing, and distribution infrastructure to commercialize any medicines for which we may obtain marketing approval; • further develop our base editing platform; • hire additional personnel, including research and development, clinical, and commercial personnel; • add operational, financial, and management information systems and personnel, including personnel to support our product development; • acquire or in-license products, intellectual property, medicines, and technologies; and • maintain and operate a commercial-scale cGMP manufacturing facility. 45 We have not completed any clinical trials of any product candidates and expect that it will be years, if ever, before we have a product candidate approved for commercialization.
We anticipate that our expenses will increase substantially if and as we: • advance clinical trials of our product candidates; • continue our research programs and our preclinical development of other product candidates from our research programs; • seek to identify additional research programs and additional product candidates; • initiate preclinical testing and clinical trials for any other product candidates we identify and develop; • maintain, expand, enforce, defend and protect our intellectual property portfolio and provide reimbursement of third-party expenses related to our patent portfolio; • seek marketing approvals for any of our product candidates that successfully complete clinical trials; 44 • establish a sales, marketing, and distribution infrastructure to commercialize any medicines for which we may obtain marketing approval; • further develop our base editing platform; • hire additional personnel, including research and development, clinical, and commercial personnel; • add operational, financial, and management information systems and personnel, including personnel to support our product development; • acquire or in-license products, intellectual property, medicines, and technologies; and • maintain and operate a commercial-scale cGMP manufacturing facility.
The success of product candidates we identify and develop will depend on many factors, including the following: • sufficiency of our financial and other resources to complete the necessary preclinical studies, IND/CTA-enabling studies, and clinical trials; • regulatory clearance of IND applications, CTAs or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for our product candidates; • successful enrollment in, and completion of, clinical trials in accordance with all applicable current Good Clinical Practice guidelines, or GCPs, current Good Laboratory Practice guidelines adopted by the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use, or ICH, and other regulatory requirements from foreign regulatory authorities; • receipt of marketing approvals and, where required, pricing and reimbursement decisions from applicable regulatory authorities; 51 • establishment of arrangements with third-party manufacturers for clinical supply and commercial manufacturing and, where applicable, commercial manufacturing capabilities; • successful development of our internal manufacturing processes and transfer to larger-scale facilities operated by either a contract manufacturing organization, or CMO, or by us; • obtaining and maintaining patent, trade secret, and other intellectual property protection and non-patent exclusivity for our medicines; • launching commercial sales of the medicines, if and when approved, whether alone or in collaboration with others; • acceptance of the products, if and when approved, by patients, the medical community, and third-party payors; • effectively competing with other therapies and treatment options; • a continued acceptable safety profile of the medicines following approval; • enforcing and defending intellectual property and proprietary rights and claims; and • supplying the product at a price that is acceptable to the pricing or reimbursement authorities in different countries.
The success of product candidates we identify and develop will depend on many factors, including the following: • sufficiency of our financial and other resources to complete the necessary preclinical studies, IND/CTA-enabling studies, and clinical trials; • regulatory clearance of IND applications, CTAs or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for our product candidates; • successful enrollment in, and completion of, clinical trials in accordance with all applicable current Good Clinical Practice guidelines, or GCPs, current Good Laboratory Practice guidelines adopted by the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use, or ICH, and other regulatory requirements from foreign regulatory authorities; • receipt of marketing approvals and, where required, pricing and reimbursement decisions from applicable regulatory authorities; • establishment of arrangements with third-party manufacturers for clinical supply and commercial manufacturing and, where applicable, commercial manufacturing capabilities; • successful development of our internal manufacturing processes and transfer to larger-scale facilities operated by either a contract manufacturing organization, or CMO, or by us; • obtaining and maintaining patent, trade secret, and other intellectual property protection and non-patent exclusivity for our medicines; • launching commercial sales of the medicines, if and when approved, whether alone or in collaboration with others; • acceptance of the products, if and when approved, by patients, the medical community, and third-party payors; • effectively competing with other therapies and treatment options; • a continued acceptable safety profile of the medicines following approval; • enforcing and defending intellectual property and proprietary rights and claims; and • supplying the product at a price that is acceptable to the pricing or reimbursement authorities in different countries. 51 If we do not successfully achieve one or more of these activities in a timely manner or at all, we could experience significant delays or an inability to successfully commercialize any product candidates we may develop, which would materially harm our business.
For example, in recent years, including in 2018 and 2019, the U.S. government shut down several times and certain regulatory agencies, such as the FDA and the SEC, had to furlough critical employees and stop critical activities. In addition, disruptions may also result from events similar to the COVID-19 pandemic.
For example, in recent years, the U.S. government shut 91 down and certain regulatory agencies, such as the FDA and the SEC, had to furlough critical employees and stop critical activities. In addition, disruptions may also result from events similar to the COVID-19 pandemic.
Future acquisitions, however, may entail numerous operational and financial risks, including: • a reduction of our current financial resources; • incurrence of substantial debt or dilutive issuances of securities to pay for acquisitions and in connection with future milestone payment obligations under such acquisition agreements; • difficulty or inability to secure financing to fund development activities for those acquired or in-licensed technologies; • higher than expected acquisition and integration costs; • disruption of our business, customer base and diversion of our management’s time and attention to develop acquired technologies; and • exposure to unknown liabilities. 100 We may not have sufficient resources to acquire businesses and technologies and integrate them into our current infrastructure.
Future acquisitions, however, may entail numerous operational and financial risks, including: • a reduction of our current financial resources; • incurrence of substantial debt or dilutive issuances of securities to pay for acquisitions and in connection with future milestone payment obligations under such acquisition agreements; • difficulty or inability to secure financing to fund development activities for those acquired or in-licensed technologies; • higher than expected acquisition and integration costs; • disruption of our business, customer base and diversion of our management’s time and attention to develop acquired technologies; and • exposure to unknown liabilities.
Finally, with the change in presidential administrations in 2025, there is substantial uncertainty as to how, if at all, the new administration will seek to modify or revise the requirements and policies of the FDA and other regulatory agencies with jurisdiction over our product candidates.
Finally, with the change in presidential administrations in 2025, there continues to be substantial uncertainty as to how the new administration will seek to modify or revise the requirements and policies of the FDA and other regulatory agencies with jurisdiction over our product candidates.
We have financed our operations primarily through private placements of our preferred stock, proceeds from sales of our common stock and collaboration revenue. We have devoted substantially all of our efforts to research and development. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future.
We have financed our operations primarily through private placements of our preferred stock, proceeds from sales of our common stock, collaboration revenue and our credit facility with Sixth Street Lending Partners. We have devoted substantially all of our efforts to research and development. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future.

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Item 2. Properties

Properties — owned and leased real estate

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Biggest changeAdditionally, we entered into a lease agreement with Alexandria Real Estate Equities, Inc. pursuant to which we built a 100,000 square foot manufacturing facility in Research Triangle Park, North Carolina intended to support a broad range of clinical programs, which lease expires in 2037.
Biggest changeAdditionally, we entered into a lease agreement with Alexandria Real Estate Equities, Inc. pursuant to which we built 107 a 100,000 square foot manufacturing facility in Research Triangle Park, North Carolina intended to support a broad range of clinical programs, which lease expires in 2037.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. Legal Proceedings. We are not currently a party to any material legal proceedings. From time to time, we may be subject to various legal proceedings and claims that arise in the ordinary course of our business activities. Item 4. Mine Safe ty Disclosures. Not Applicable. 107 PART II
Biggest changeItem 3. Legal Proceedings. We are not currently a party to any material legal proceedings. From time to time, we may be subject to various legal proceedings and claims that arise in the ordinary course of our business activities. Item 4. Mine Safe ty Disclosures. Not Applicable. 108 PART II

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Mine Safety Disclosures 107 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 108 Item 6. [Reserved] 110 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 111 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 123 Item 8.
Biggest changeItem 4. Mine Safety Disclosures 108 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 109 Item 6. [Reserved] 110 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 111 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 124 Item 8.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeWe intend to retain future earnings, if any, to finance the operation and expansion of our business and do not anticipate paying any cash dividends to holders of common stock in the foreseeable future. 108 Stock Performance Graph The following performance graph and related information shall not be deemed to be “soliciting material” or to be “filed” with the Securities and Exchange Commission, or SEC, for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, nor shall such information be incorporated by reference into any future filing under the Exchange Act or Securities Act of 1933, as amended, or the Securities Act, except to the extent that we specifically incorporate it by reference into such filing.
Biggest changeIn addition, our financing agreement with Sixth Street Lending Partners contains restrictive covenants that prohibit us, subject to certain exceptions, from paying dividends on our common stock, and future debt securities or other financing arrangements could contain similar or more restrictive negative covenants. 109 Stock Performance Graph The following performance graph and related information shall not be deemed to be “soliciting material” or to be “filed” with the Securities and Exchange Commission, or SEC, for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, nor shall such information be incorporated by reference into any future filing under the Exchange Act or Securities Act of 1933, as amended, or the Securities Act, except to the extent that we specifically incorporate it by reference into such filing.
Holders As of February 18, 2025, there were approximately 27 holders of record of our common stock. This number does not include beneficial owners whose shares are held by nominees in street name. Dividends We have not declared or paid any cash dividends on our capital stock since our inception.
Holders As of February 17, 2026, there were approximately 25 holders of record of our common stock. This number does not include beneficial owners whose shares are held by nominees in street name. Dividends We have not declared or paid any cash dividends on our capital stock since our inception.
The graph set forth below compares the cumulative total stockholder return on our shares of common stock between February 6, 2020 (the date of our initial public offering) and December 31, 2024, with the cumulative total return of (a) the Nasdaq Biotechnology Index and (b) the Nasdaq Composite Index, over the same period.
The graph set forth below compares the cumulative total stockholder return on our shares of common stock between December 31, 2020 and December 31, 2025, with the cumulative total return of (a) the Nasdaq Biotechnology Index and (b) the Nasdaq Composite Index, over the same period.
The stock price performance included in this graph is not necessarily indicative of future stock price performance. 109 Purchases of equity securities by the issuer or affiliated purchasers Neither we nor any affiliated purchaser or anyone acting on our behalf or on behalf of an affiliated purchaser made any purchases of shares of our common stock during the fourth quarter of 2024.
Purchases of equity securities by the issuer or affiliated purchasers Neither we nor any affiliated purchaser or anyone acting on our behalf or on behalf of an affiliated purchaser made any purchases of shares of our common stock during the fourth quarter of 2025.
This graph assumes the investment of $100 on February 6, 2020 in our common stock, the Nasdaq Biotechnology Index and the Nasdaq Composite Index and assumes the reinvestment of dividends, if any.
This graph assumes the investment of $100 on December 31, 2020 in our common stock, the Nasdaq Biotechnology Index and the Nasdaq Composite Index and assumes the reinvestment of dividends, if any. The comparisons shown in the graph below are based upon historical data.
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The graph uses the closing sales price of our common stock of $18.75 per share on February 6, 2020 as the initial value of our common stock and not the initial offering price to the public of $17.00 per share. The comparisons shown in the graph below are based upon historical data.
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We intend to retain future earnings, if any, to finance the operation and expansion of our business and do not anticipate paying any cash dividends to holders of common stock in the foreseeable future.
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The stock price performance included in this graph is not necessarily indicative of future stock price performance.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe following table summarizes our research and development expenses for the years ended December 31, 2024 and December 31, 2023, together with the changes in those items in dollars (in thousands): Years Ended December 31, 2024 2023 Change External research and development expenses $ 114,473 $ 154,178 $ (39,705 ) Employee related expenses 98,796 109,878 (11,082 ) Facility and information technology related expenses 73,387 69,339 4,048 Stock-based compensation expense 73,522 57,812 15,710 Other expense (income) 7,383 46,174 (38,791 ) Total research and development expenses $ 367,561 $ 437,381 $ (69,820 ) The decrease of $69.8 million was primarily due to the following: • A $39.7 million decrease in external research and development expenses driven by a $29.6 million decrease in outsourced services, primarily due to the strategic reprioritization of pipeline programs, timing of manufacturing spend and fewer IND-enabling activities, partially offset by increased clinical activities.
Biggest changeThe following table summarizes our research and development expenses for the years ended December 31, 2025 and December 31, 2024, together with the changes in those items in dollars (in thousands): Year Ended December 31, 2025 2024 Change External research and development expenses $ 142,376 $ 114,473 $ 27,903 Employee related expenses 117,366 98,796 18,570 Facility and information technology related expenses 77,146 73,387 3,759 Stock-based compensation expenses 56,123 73,522 (17,399 ) In-process research and development expenses 14,507 — 14,507 Other expenses 2,100 7,383 (5,283 ) Total research and development expenses $ 409,618 $ 367,561 $ 42,057 The increase of $42.1 million was primarily due to the following: • An increase of $27.9 million in external research and development expenses driven by a $29.0 million increase in outsourced services, primarily due to increased clinical and manufacturing activities, slightly offset by a $1.1 million decrease in lab supply expenses due to the advancement of pipeline programs and a shift of programs beyond research activities; • An increase of $18.6 million of employee related expenses due to the increase in the number of research and development employees between December 31, 2024 and December 31, 2025 and annual compensation increases; • An increase of $14.5 million due to a one-time in-process research and development charge associated with assets acquired from our acquisition of an early-stage life sciences company during the year ended December 31, 2025 that were determined to have no alternative future use; and • An increase of $3.8 million of facility and information technology, or IT, related costs, including depreciation and the expense allocated to research and development related to our leased facilities.
We believe this design contributes to a more precise and efficient edit compared to traditional gene editing methods, with the potential to dramatically increase the impact of gene editing. We are also pursuing a suite of both delivery modalities, including both ex vivo and in vivo approaches, depending on tissue type.
We believe this design contributes to a more precise and efficient edit compared to traditional gene editing methods, with the potential to dramatically increase the impact of gene editing. We are also pursuing a suite of delivery modalities, including both ex vivo and in vivo approaches, depending on tissue type.
The elegance of the base editing approach, combined with a tissue specific delivery modality, provides the basis for a targeted, efficient, precise, and highly versatile gene editing system that is designed to be capable of gene correction, gene silencing or gene activation, gene modification, and/or multiplex editing of several genes simultaneously.
The elegance of the base editing approach, combined with a tissue specific delivery modality, provides the basis for a targeted, efficient, precise, and highly versatile gene editing system that is designed to be capable of gene correction, gene silencing, gene activation, gene modification, and/or multiplex editing of several genes simultaneously.
This point mutation causes Alpha-1 antitrypsin, or AAT, to misfold, accumulating inside liver cells rather than being secreted, resulting in very low levels (10%-15%) of circulating AAT. In addition to resulting in lower levels, the PiZ AAT protein variant is also less enzymatically effective compared to wildtype AAT protein.
This point mutation causes Alpha-1 antitrypsin, or AAT, protein to misfold, accumulating inside liver cells rather than being secreted, resulting in very low levels (10%-15%) of circulating AAT. In addition to resulting in lower levels, the PiZ AAT protein variant is also less enzymatically effective compared to wildtype AAT protein.
Investing activities For the year ended December 31, 2024, cash provided by investing activities of $185.0 million was primarily the result of net maturities of marketable securities partially offset by purchases of marketable securities, in addition to purchases of property and equipment of $8.9 million.
For the year ended December 31, 2024, cash provided by investing activities of $185.0 million was primarily the result of net maturities of marketable securities partially offset by purchases of marketable securities, in addition to purchases of property and equipment of $8.9 million.
Specifically, our expenses will increase if and as we: • advance clinical trials of our product candidates; • continue our research programs and our preclinical development of product candidates from our research programs; • seek to identify additional research programs and additional product candidates; • initiate preclinical studies and clinical trials for additional product candidates we identify and develop; • seek marketing approvals for any of our product candidates that successfully complete clinical trials; • establish a sales, marketing, and distribution infrastructure to commercialize any medicines for which we may obtain marketing approval; • maintain, expand, enforce, defend, and protect our intellectual property portfolio and provide reimbursement of third-party expenses related to our patent portfolio; • further develop our base editing platform; • continue to hire additional personnel including research and development, clinical and commercial personnel; • add operational, financial, and management information systems and personnel, including personnel to support our product development; • acquire or in-license products, intellectual property, medicines and technologies; and • maintain and operate a commercial-scale cGMP manufacturing facility.
Specifically, our expenses will increase if and as we: • advance clinical trials of our product candidates; • continue our research programs and our preclinical development of product candidates from our research programs; • maintain and operate a commercial-scale cGMP manufacturing facility; • seek to identify additional research programs and additional product candidates; • initiate preclinical studies and clinical trials for additional product candidates we identify and develop; • seek marketing approvals for any of our product candidates that successfully complete clinical trials; • establish a sales, marketing, and distribution infrastructure to commercialize any medicines for which we may obtain marketing approval; • maintain, expand, enforce, defend, and protect our intellectual property portfolio and provide reimbursement of third-party expenses related to our patent portfolio; • further develop our base editing platform; • continue to hire additional personnel including research and development, clinical and commercial personnel; • add operational, financial, and management information systems and personnel, including personnel to support our product development; and • acquire or in-license products, intellectual property, medicines and technologies.
A significant change in our stock price or volatility could have a significant impact on the value of the liability. Accrued and prepaid research and development costs As part of the process of preparing our financial statements, we are required to estimate our accrued expenses and prepaid research and development costs.
A significant change in our stock price or volatility could have a significant impact on the value of the liability. Accrued and prepaid research and development costs 123 As part of the process of preparing our financial statements, we are required to estimate our accrued expenses and prepaid research and development costs.
In September 2022, we entered into a License and Research Collaboration Agreement, or the 113 Orbital Agreement, with Orbital Therapeutics, Inc., or Orbital, a newly formed entity focused on advancing non-viral delivery and RNA technologies.
In September 2022, we entered into a License and Research Collaboration Agreement, or the Orbital Agreement, with Orbital Therapeutics, Inc., or Orbital, a newly formed entity focused on advancing non-viral delivery and RNA technologies.
Research and development expenses Research and development expenses consist of costs incurred in performing research and development activities, which include: • expenses incurred in connection with our clinical trials, including contract research organization costs and costs related to study preparation; • the cost of manufacturing materials for use in our preclinical studies, IND-enabling studies and clinical trials; • expenses incurred in connection with investments in delivery technology for our base editors; • expenses incurred in connection with the discovery and preclinical development of our research programs, including under agreements with third parties, such as consultants, contractors and contract research organizations; • personnel-related expenses, including salaries, bonuses, benefits and stock-based compensation for employees engaged in research and development functions; • the cost to obtain licenses to intellectual property, such as those with Harvard University, or Harvard, The Broad Institute, Inc., or Broad Institute, Editas Medicine, Inc., or Editas, and Bio Palette Co., Ltd., or Bio Palette, and related future payments should certain success, development and regulatory milestones be achieved; • expenses incurred in connection with the building of our base editing platform; • expenses incurred in connection with regulatory filings; • laboratory supplies and research materials; and • facilities, depreciation and other expenses which include direct and allocated expenses.
Research and development expenses Research and development expenses consist of costs incurred in performing research and development activities, which include: • expenses incurred in connection with our clinical trials, including contract research organization costs and costs related to study preparation; • the cost of manufacturing materials for use in our preclinical studies, our IND enabling studies and clinical trials; • expenses incurred in connection with investments in delivery technology for our base editors; • expenses incurred in connection with the discovery and preclinical development of our research programs, including under agreements with third parties, such as consultants, contractors and contract research organizations; • personnel-related expenses, including salaries, bonuses, benefits and stock-based compensation for employees engaged in research and development functions; • the cost to obtain licenses to intellectual property, such as those with Harvard University, or Harvard, The Broad Institute, Inc., or Broad Institute, Editas Medicine, Inc., or Editas, and Bio Palette Co., Ltd., or Bio Palette, and related future payments should certain success, development and regulatory milestones be achieved; • expenses incurred in connection with the building of our base editing platform; • expenses to acquire in-process research and development with no alternative future use; • expenses incurred in connection with regulatory filings; • laboratory supplies and research materials; and • facilities, depreciation and other expenses which include direct and allocated expenses.
We expect that our cash, cash equivalents, and marketable securities at December 31, 2024 will enable us to fund our current and planned operating expenses and capital expenditures for at least the next 12 months from the date of issuance of our accompanying consolidated financial statements.
We expect that our cash, cash equivalents, and marketable securities at December 31, 2025 will enable us to fund our current and planned operating expenses and capital expenditures for at least the next 12 months from the date of issuance of our accompanying consolidated financial statements.
Our future funding requirements will depend on many factors including: • the cost of continuing to build our base editing platform; • the costs of acquiring licenses for the delivery modalities that will be used with our product candidates; • the scope, progress, results, and costs of discovery, preclinical development, laboratory testing, manufacturing and clinical trials for the product candidates we may develop; • the costs of preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights, and defending intellectual property-related claims; • the costs, timing, and outcome of regulatory review of the product candidates we develop; • the costs of future activities, including product sales, medical affairs, marketing, manufacturing, distribution, coverage and reimbursement for any product candidates for which we receive regulatory approval; • the success of our license agreements and our collaborations; • our ability to establish and maintain additional collaborations on favorable terms, if at all; • the achievement of milestones or occurrence of other developments that trigger payments under any collaboration agreements we are a party to or may become a party to, including our agreement with Guide; • the payment of success liabilities to Harvard and Broad Institute pursuant to the respective terms of the Harvard License Agreement and the Broad Institute License Agreement, should we choose to pay in cash; • the extent to which we acquire or in-license products, intellectual property, and technologies; • the costs of operating and expanding our manufacturing capacity; and 119 • the impact on our business of macro-economic conditions, as well as the prevailing level of macro-economic, business, and operational uncertainty, including as a result of geopolitical events or other global or regional events.
Our future funding requirements will depend on many factors including: • the cost of continuing to build our base editing platform; • the costs of acquiring licenses for the delivery modalities that will be used with our product candidates; • the scope, progress, results, and costs of discovery, preclinical development, laboratory testing, manufacturing and clinical trials for the product candidates we may develop; 120 • the costs of operating and expanding our manufacturing capacity; • the costs of preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights, and defending intellectual property-related claims; • the costs, timing, and outcome of regulatory review of the product candidates we develop; • the costs of future activities, including product sales, medical affairs, marketing, manufacturing, distribution, coverage and reimbursement for any product candidates for which we receive regulatory approval; • the success of our license agreements and our collaborations; • our ability to establish and maintain additional collaborations on favorable terms, if at all; • the achievement of milestones or occurrence of other developments that trigger payments under any collaboration agreements we are a party to or may become a party to; • the payment of success liabilities to Harvard and Broad Institute pursuant to the respective terms of the Harvard License Agreement and the Broad License Agreement, should we choose to pay in cash; • the extent to which we acquire or in-license products, intellectual property, and technologies; and • the impact on our business of macro-economic conditions, as well as the prevailing level of macro-economic, business, and operational uncertainty, including as a result of geopolitical events, the imposition of new or revised global trade tariffs or other global or regional events.
Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances, and licensing arrangements. We may be unable to raise additional funds or enter into such other agreements when needed on favorable terms or at all.
Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of equity offerings, debt financings, including our Credit Facility, collaborations, strategic alliances, and licensing arrangements. We may be unable to raise additional funds or enter into such other agreements when needed on favorable terms or at all.
Results of operations For discussion of 2023 results and comparison with 2022 results, refer to Part II, Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2023.
Results of operations For discussion of 2024 results and comparison with 2023 results, refer to Part II, Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024.
We agreed to pay Jefferies a commission of up to 3.0% of the aggregate gross sale proceeds of any shares sold by Jefferies under the Sales Agreement. There were no shares sold under the Sales Agreement during the year ended December 31, 2024.
We agreed to pay Jefferies a commission of up to 3.0% of the aggregate gross sale proceeds of any shares sold by Jefferies under the Sales Agreement. There were no shares sold under the Sales Agreement during the year ended December 31, 2025.
General and administrative expenses General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in our executive, intellectual property, business development and administrative functions.
General and administrative expenses General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in our executive, intellectual property, business development, commercial readiness and administrative functions.
GSD1a is an autosomal recessive disorder caused by mutations in the G6PC gene that disrupts a key enzyme, G6Pase, critical for 112 maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can result in seizures and be fatal.
GSDIa is an autosomal recessive disorder caused by mutations in the G6PC gene that disrupts a key enzyme, G6Pase, critical for maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can result in seizures and be fatal.
Financing activities Net cash provided by financing activities for the year ended December 31, 2024 of $7.7 million consisted of proceeds from the exercise of stock options of $5.6 million and $2.6 million of proceeds from the issuance of common stock under our Employee Stock Purchase Plan, or ESPP, offset in part by net repayments of equipment financing liabilities of $0.5 million.
Net cash provided by financing activities for the year ended December 31, 2024 of $7.7 million consisted of proceeds from the exercise of stock options of $5.6 million and $2.6 million of proceeds from the issuance of common stock under our ESPP, offset in part by net repayments of equipment financing liabilities of $0.5 million.
BEAM-101 is a patient-specific, autologous HSC investigational therapy designed to offer a potentially best-in-class profile, incorporating base edits that are intended to mimic single nucleotide polymorphisms seen in individuals with hereditary persistence of fetal hemoglobin, or HbF.
Risto-cel is a patient-specific, autologous HSC investigational therapy designed to offer a potentially best-in-class profile, incorporating base edits that are intended to mimic single nucleotide polymorphisms seen in individuals with hereditary persistence of fetal hemoglobin, or HbF.
To date, we have not generated any revenue from product sales and do not expect to generate revenue from the sale of products for the foreseeable future. Our revenue to date has been primarily derived from license and collaboration agreements with partners. Since inception we have incurred significant operating losses.
To date, we have not generated any revenue from product sales and do not expect to generate revenue from the sale of products in the near future. Our revenue to date has been primarily derived from license and collaboration agreements with partners. Since inception we have incurred significant operating losses.
BEAM-301: In Vivo LNP liver-targeting for GSD1a BEAM-301 is a liver-targeting LNP formulation of base editing reagents designed to correct the R83C mutation, the most prevalent disease-causing mutation for, and the mutation which results in the most severe form of, glycogen storage disease 1a, or GSD1a.
BEAM-301: In Vivo LNP liver-targeting for GSDIa BEAM-301 is a liver-targeting LNP formulation of base editing reagents designed to correct the R83C mutation, the most prevalent disease-causing mutation for, and the mutation which results in the most severe form of, glycogen storage disease Ia, or GSDIa.
We have not generated any revenue to date from product sales and do not expect to do so in the near future. During the years ended December 31, 2024, 2023, and 2022, we recognized $63.5 million, $377.7 million and $60.9 million respectively, of revenue from our license and collaboration agreements.
We have not generated any revenue to date from product sales and do not expect to do so in the near future. During the years ended December 31, 2025, 2024, and 2023, we recognized $139.7 million, $63.5 million and $377.7 million respectively, of revenue from our license and collaboration agreements.
License and collaboration revenue recorded in 2024 represents revenue recorded under the Pfizer, Apellis and Orbital Agreements, as well as $27.0 million of revenue recognized from development and regulatory milestones achieved under our agreements with Lilly and Sana.
License and collaboration revenue recorded in 2025 represents revenue recorded under the Pfizer, Apellis and Orbital Agreements. License and collaboration revenue recorded in 2024 represents revenue recorded under the Pfizer, Apellis and Orbital Agreements, as well as $27.0 million of revenue recognized from development and regulatory milestones achieved under our agreements with Lilly and Sana Biotechnology, Inc, or Sana.
Our agreements to license intellectual property include potential milestone payments that are dependent upon the development of products using the intellectual property licensed under the agreements and contingent upon the achievement of development or regulatory approval milestones, as well as commercial and success payment milestones.
These agreements include potential milestone payments that are dependent upon the development of products using the intellectual property licensed under the agreements and contingent upon the achievement of development or regulatory approval milestones, as well as commercial and success payment milestones.
For our initial clinical trials, we expect to rely primarily on our internal manufacturing capabilities, along with CMOs with relevant manufacturing experience in genetic medicines. We believe this investment will maximize the value of our portfolio and capabilities, the probability of technical success of our programs, and the speed at which we can provide potentially life-long cures to patients.
For our current clinical trials, we are relying primarily on our internal manufacturing capabilities, along with CMOs with relevant manufacturing experience in genetic medicines. We believe this investment will maximize the value of our portfolio and capabilities, the probability of technical success of our programs, and the speed at which we can provide potentially life-long cures to patients.
Information pertaining to fiscal year 2022 was included in our Annual Report on Form 10-K for the year ended December 31, 2023 on pages 115 through 126 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 27, 2024.
Information pertaining to fiscal year 2023 was included in our Annual Report on Form 10-K for the year ended December 31, 2024 on pages 111 through 123 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 25, 2025.
Our net losses for the years ended December 31, 2024, 2023 and 2022 were $376.7 million, $132.5 million and $289.1 million, respectively. As of December 31, 2024, we had an accumulated deficit of $1.6 billion.
Our net losses for the years ended December 31, 2025, 2024 and 2023 were $80.0 million, $376.7 million and $132.5 million, respectively. As of December 31, 2025, we had an accumulated deficit of $1.6 billion.
Research and development expenses are expected to continue to increase as we advance clinical trials for BEAM-101, BEAM-302, and BEAM-301, continue our current research programs, initiate new research programs, continue the preclinical and clinical development of our product candidates, conduct any future preclinical studies, and begin to enroll patients in and conduct clinical trials for any of our product candidates.
Research and development expenses are expected to continue to increase as we advance clinical trials for risto-cel, BEAM-302, and BEAM-304, continue our current research programs, initiate new research programs, continue the preclinical and clinical development of our product candidates, conduct any future preclinical studies, and enroll patients in and conduct clinical trials for any of our product candidates.
The leases relate primarily to office space, laboratory and manufacturing space, and equipment. Aggregate future minimum commitments under these office and laboratory leases and equipment leases are $227.7 million as of December 31, 2024, excluding any related common area maintenance charges or real estate taxes.
The leases relate primarily to office space, laboratory and manufacturing space, and equipment. Aggregate future minimum commitments under these office and laboratory leases and equipment leases are $210.1 million as of December 31, 2025, excluding any related common area maintenance charges or real estate taxes.
We have not yet commercialized any of our product candidates, and we do not expect to generate revenue from the sale of our product candidates for the foreseeable future.
We have not yet commercialized any of our product candidates, and we do not expect to generate revenue from the sale of our product candidates in the near future.
To date, we have financed our operations primarily through the sales of our redeemable convertible preferred stock, proceeds from offerings of our common stock and payments received under collaboration and license agreements. We are an early-stage company, and the majority of our programs are at a preclinical or clinical stage of development.
To date, we have financed our operations primarily through the sales of our redeemable convertible preferred stock, proceeds from offerings of our common stock, payments received under collaboration and license agreements, and our credit facility with Sixth Street Lending Partners. We are an early-stage company, and our programs are at a preclinical or clinical stage of development.
It is estimated that approximately 100,000 individuals in the United States have two copies of the Z allele. There are currently no curative treatments for patients with AATD. We are conducting a Phase 1/2 open label, dose escalation clinical trial of BEAM-302 at sites located in the United Kingdom for the treatment of AATD.
It is estimated that approximately 100,000 individuals in the United States have two copies of the Z allele. There are currently no curative treatments for patients with AATD. 112 We are conducting a Phase 1/2 open label, dose exploration and dose expansion clinical trial of BEAM-302 for the treatment of AATD.
General and administrative expenses General and administrative expenses were $111.5 million and $116.8 million for the years ended December 31, 2024 and 2023, respectively.
General and administrative expenses General and administrative expenses were $113.8 million and $111.5 million for the years ended December 31, 2025 and 2024, respectively.
As of December 31, 2024, we have sold 13,769,001 shares of our common stock under the Sales Agreement at an average price of $62.75 per share for aggregate gross proceeds of $864.0 million, before deducting commissions and offering expenses payable by us. As of December 31, 2024, we had $850.7 million in cash, cash equivalents, and marketable securities.
As of December 31, 2025, we have sold 13,769,001 shares of our common stock under the Sales Agreement at an average price of $62.75 per share for aggregate gross proceeds of $864.0 million, before deducting commissions and offering expenses payable by us.
These contracts generally provide for termination on notice, and therefore are cancelable contracts. Critical accounting policies and significant judgments and estimates Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles.
Critical accounting policies and significant judgments and estimates Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles.
Once reinfused, the HSCs begin repopulating a portion of the bone marrow in a process known as engraftment. The engrafted, edited HSCs give rise to progenitor cell types with the corrected gene sequences. We are deploying this ex vivo approach in our BEAM-101 and ESCAPE base editing programs.
Once reinfused, the HSCs begin repopulating a portion of the bone marrow in a process known as engraftment. The engrafted, edited HSCs give rise to progenitor cell types with the corrected gene sequences. We are deploying this ex vivo approach in our risto-cel program.
Wave 1: Ex Vivo Base Editing via Autologous Transplant with BEAM-101 We are using base editing to pursue the development of BEAM-101 for the treatment of sickle cell disease.
Ex Vivo Base Editing via Autologous Transplant with risto-cel We are using base editing to pursue the development of risto-cel for the treatment of sickle cell disease.
Our actual results may differ from these estimates under different assumptions or conditions. 120 While our significant accounting policies are described in more detail in Note 2 to our consolidated financial statements in this Annual Report on Form 10-K, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our financial statements.
While our significant accounting policies are described in more detail in Note 2 to our consolidated financial statements in this Annual Report on Form 10-K, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our financial statements.
Hematology We are advancing hematology base editing programs in which hematopoietic stem cells, or HSCs, are collected from a patient, edited using electroporation, and then infused back into the patient following a conditioning regimen, such as treatment with busulfan, the standard of care in HSC transplantation, or HSCT, today.
Our initial wave consists of ex vivo programs in which hematopoietic stem cells, or HSCs, are collected from a patient, edited using electroporation, and then infused back into the patient following a conditioning regimen, such as treatment with busulfan, the standard of care in HSC transplantation, or HSCTs, today.
The BEACON trial initially includes up to 45 patients ages 18 to 35 with severe sickle cell disease who have received prior treatment with at least one disease-modifying agent with inadequate response or intolerance. Following mobilization, conditioning and treatment with BEAM-101, patients are assessed for safety and tolerability, with safety endpoints including neutrophil and platelet engraftment.
The BEACON trial includes approximately 50 adults and adolescents with severe sickle cell disease who have received prior treatment with at least one disease-modifying agent with inadequate response or intolerance. Following mobilization, conditioning and treatment with risto-cel, patients are assessed for safety and tolerability, with safety endpoints including neutrophil and platelet engraftment.
We can give no assurance that we will be able to secure such additional sources of capital to support our operations, or, if such capital is available to us, that such additional capital will be sufficient to meet our needs for the short or long term.
We can give no assurances that we will be able to secure such additional sources of capital to support our operations, or, if such funds are available to us, that such additional financing will be sufficient to meet our needs.
Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends.
The Financing Agreement includes covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends, and future debt financings, if available, may include similar restrictions.
Change in fair value of non-controlling equity investments During the years ended December 31, 2024 and 2023, we recorded other expense of $14.1 million and $18.6 million, respectively, as a result of changes in the fair value of our investments in Verve and Prime Medicine common stock.
Change in fair value of non-controlling equity investments During the years ended December 31, 2025 and 2024, we recorded other income of $3.9 million and other expense of $14.1 million, respectively, as a result of changes in the fair value of our investments in corporate equity securities.
The trial is an open-label, multi-cohort, single-ascending dose evaluation of BEAM-301 for the treatment of GSD1a in patients with the R83C mutation. Key endpoints of the trial include safety and tolerability, time to hypoglycemia during fasting, and changes from baseline in corn starch supplementation. We are continuing site activation activities and expect dosing to commence in early 2025.
The trial is an open-label, multi-cohort, single-ascending dose evaluation of BEAM-301 for the treatment of GSDIa in patients with the R83C mutation. Key endpoints of the trial include safety and tolerability, time to hypoglycemia during fasting, and changes from baseline in corn starch supplementation. Dosing is complete in the first cohort, and enrollment has been initiated in the second cohort.
Interest and other income (expense), net Interest and other income (expense), net was $49.1 million and $46.7 million of other income for the years ended December 31, 2024 and December 31, 2023, respectively. The increase was primarily due to increases in interest income driven by increased market rates and growth of our investment portfolio.
Interest and other income (expense), net Interest and other income (expense), net was $43.7 million and $49.1 million of other income for the years ended December 31, 2025 and December 31, 2024, respectively. The decrease was primarily due to decreases in interest income offset slightly by the growth of our investment portfolio.
We believe this suite of technologies – base editing, improved conditioning and in vivo delivery for editing HSCs – can maximize the potential applicability of our sickle cell disease programs to patients as well as create a platform for the treatment of many other severe genetic blood disorders.
We are also pursuing a next wave of in vivo base editing with delivery directly into HSCs of patients via LNPs. We believe this multi-wave strategy can maximize the potential applicability of our sickle cell disease programs to patients as well as create a platform for the treatment of many other severe genetic blood disorders.
General and administrative expenses also include legal fees relating to intellectual property and corporate matters, professional fees for accounting, auditing, tax and consulting services, insurance costs, travel, and direct and allocated facility related expenses and other operating costs. We anticipate that our general and administrative expenses will increase in the future to support our increased research and development activities.
General 115 and administrative expenses also include legal fees relating to intellectual property and corporate matters, professional fees for accounting, auditing, tax and consulting services, insurance costs, travel, and direct and allocated facility related expenses and other operating costs.
We do not have any committed external source of capital. We have historically relied on equity issuances to fund our capital needs and will likely rely on equity issuances in the future.
Other than the Credit Facility, we do not have any committed external source of capital. We have historically relied on equity issuances and collaboration revenue to fund our capital needs.
In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period and adjust accordingly.
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. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period and adjust accordingly.
These payments are contingent upon the occurrence of future events and the timing and likelihood of such potential obligations are not known with certainty. Additionally, we enter into contracts in the normal course of business with CROs, CMOs and other vendors to assist in the performance of our research and development activities and other services and products for operating purposes.
Additionally, we enter into contracts in the normal course of business with CROs, CMOs and other vendors to assist in the performance of our research and development activities and other services and products for operating purposes. These contracts generally provide for termination on notice, and therefore are cancelable contracts.
Determining the revenue recognition of IP licenses requires significant judgment and is discussed in further detail for each of our license and collaboration agreements in Notes 9 and 10 . 121 Milestone payments: At the inception of each arrangement that includes development or regulatory milestone payments, we evaluate the probability of reaching the milestones and estimate the amount to be included in the transaction price using the most likely amount method.
Milestone payments: At the inception of each arrangement that includes development or regulatory milestone payments, we evaluate the probability of reaching the milestones and estimate the amount to be included in the transaction price using the most likely amount method.
These uses of cash were partially offset by increases in accounts payable of $1.8 million and other long-term liabilities of $0.5 million, as well as noncash items, including stock-based compensation expense of $120.7 million, depreciation and amortization expense of $21.9 million, a decrease in the fair value of non-controlling equity investments of $14.1 million and a decrease in operating lease right-of-use, or ROU, assets of $9.7 million.
These uses of cash were partially offset by increases in accounts payable of $1.8 million and other long-term liabilities of $0.5 million, as well as noncash items, including stock-based compensation expense of $120.7 million, depreciation and amortization expense of $21.9 million, a decrease in the fair value of non-controlling equity investments of $14.1 million and a decrease in operating lease right-of-use, or ROU, assets of $9.7 million. 119 Investing activities For the year ended December 31, 2025, cash used in investing activities of $121.4 million was primarily driven by net purchases of marketable securities of $367.3 million, purchases of property and equipment of $15.0 million and the payment of $0.1 million of equity issuance costs associated with our acquisition of an early-stage life sciences company.
We may additionally owe Harvard and Broad Institute success payments of up to an additional $90.0 million each. We are potentially obligated to pay certain milestone and success fees, non-royalty sublicense income fees, royalty fees, licensing maintenance fees, and reimbursement of patent maintenance costs under agreements we have entered into with certain institutions to license intellectual property.
We are potentially obligated to pay certain milestone and success fees, non-royalty sublicense income fees, royalty fees, licensing maintenance fees, and reimbursement of patent maintenance costs under agreements to license intellectual property.
A portion of the success payments was paid in June 2021; the remaining success payment obligations are still outstanding as of December 31, 2024 and will continue to be revalued at each reporting period.
There were no success payment obligations paid during the years ended December 31, 2025, 2024 or 2023. The success payment obligations are still outstanding as of December 31, 2025 and will continue to be revalued at each reporting period.
We also expect to continue to incur costs associated with being a public company and maintaining controls over financial reporting, including costs of accounting, audit, legal, regulatory and tax-related services associated with maintaining compliance with Nasdaq and SEC requirements, director and officer insurance costs, and investor and public relations costs. 114 Other income and expenses Other income and expenses consist of the following items: • Change in fair value of derivative liabilities consists primarily of remeasurement gains or losses associated with changes in success payment liabilities associated with our license agreement with Harvard, dated as of June 27, 2017, as amended, or the Harvard License Agreement, the license agreement with The Broad Institute, as amended, dated as of May 9, 2018, or the Broad License Agreement, and settlement payment derivative liabilities associated with a settlement agreement with a research institution. • Change in fair value of non-controlling equity investments consists of changes in the fair value of our investments in equity securities. • Change in fair value of contingent consideration liabilities consists of remeasurement of the fair market value of the technology and product contingent consideration liabilities related to the acquisition of Guide. • Interest and other income (expense), net consists primarily of interest income from our investments in fixed income securities as well as interest expense related to our equipment financings.
Other income and expenses Other income and expenses consist of the following items: • Change in fair value of derivative liabilities consists primarily of remeasurement gains or losses associated with changes in success payment liabilities associated with our license agreement with Harvard, dated as of June 27, 2017, as amended, or the Harvard License Agreement and the license agreement with The Broad Institute, as amended, dated as of May 9, 2018, or the Broad License Agreement. • Change in fair value of non-controlling equity investments consists of changes in the fair value of our investments in equity securities. • Change in fair value of contingent consideration liabilities consists of remeasurement of the fair value of the milestone payments associated with our contingent consideration liabilities from acquisitions. • Interest and other income (expense), net consists primarily of interest income from our investments in fixed income securities as well as interest expense related to our equipment financings.
Examples of estimated accrued research and development expenses include fees paid to vendors in connection with preclinical development activities and vendors related to development, manufacturing and distribution of product candidate materials. 122 We base our expenses related to preclinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple vendors that conduct and manage preclinical studies on our behalf.
Examples of estimated accrued research and development expenses include fees paid to vendors in connection with preclinical development activities and vendors related to development, manufacturing and distribution of product candidate materials.
Overall, we are seeking to build the leading integrated platform for precision genetic medicine, which may have broad therapeutic applicability and the potential to transform the field of precision genetic medicines.
Overall, we are seeking to build the leading integrated platform for precision genetic medicine, which may have broad therapeutic applicability and the potential to transform the field of precision genetic medicines. Hematology We are pursuing a long-term, staged development strategy for our base editing approach to treat hematological diseases, such as sickle cell disease and beta-thalassemia.
If the entity does not satisfy a performance obligation over time, the related performance obligation is satisfied at a point in time by transferring the control of a promised good or service to a customer.
If the entity does not satisfy a performance obligation over time, the related performance obligation is satisfied at a point in time by transferring the control of a promised good or service to a customer. 122 The timing of when services are performed and the occurrence of external costs associated with the programs under the collaboration agreements could impact how revenue is recognized in a certain period.
BEAM-101 aims to alleviate the effects of sickle cell disease by increasing HbF, which is expected to increase functional hemoglobin production and, in the case of sickle cell disease, inhibit hemoglobin S, or HbS, polymerization. 111 We are conducting a Phase 1/2 clinical trial designed to assess the safety and efficacy of BEAM-101 for the treatment of sickle cell disease, which we refer to as our BEACON trial.
We are conducting a Phase 1/2 clinical trial designed to assess the safety and efficacy of risto-cel for the treatment of sickle cell disease, which we refer to as our BEACON trial.
Provision for income taxes We recorded an income tax provision of less than $0.1 million for the year ended December 31, 2024 and a provision of $1.4 million for the year ended December 31, 2023, which reflects that we generated taxable income that was not fully offset by the use of tax operating loss carryforwards and tax credits.
Provision for income taxes We did not record an income tax provision for the year ended December 31, 2025 and recorded an income tax provision of less than $0.1 million for the year ended December 31, 2024.
The decrease in revenue is driven primarily by $216.4 million of up-front revenue recognized in the year ended December 31, 2023, from the transaction with Lilly (see Note 10) and the net change in activity amongst our collaboration agreements.
The increase in revenue is driven primarily by $109.1 million of revenue recognized in the year ended December 31, 2025, due to the completion of our collaboration deal with Pfizer and the net change in activity amongst our other collaboration agreements.
Change in contingent consideration liabilities During the years ended December 31, 2024 and 2023, we recorded $1.6 million and $9.7 million, respectively, of other income related to the change in fair value of the Guide technology and product contingent consideration liabilities as a result of an update in project timelines and the expected probability of achievement of the milestones.
Change in contingent consideration liabilities During the years ended December 31, 2025 and 2024, we recorded $0.2 million and $1.6 million, respectively, of other income related to the change in fair value of the milestone payments related to our contingent consideration liabilities from acquisitions.
Patients are also assessed for efficacy, with efficacy endpoints including the change from baseline in severe vaso-occlusive events, transfusion requirements, HbF levels, and quality of life assessments. In December 2024, we announced preliminary positive data from our Phase 1/2 clinical trial of BEAM-101, which we refer to as the BEACON trial.
Patients are also assessed for efficacy, with efficacy endpoints including the change from baseline in severe vaso-occlusive events, transfusion requirements, HbF levels, and quality of life assessments. The adult and adolescent enrollment for BEACON is complete, and manufacturing of all doses was completed as of 111 December 2025. The U.S.
Revenue recognition In April 2019, we entered into a collaboration and license agreement, or the Verve Agreement, with Verve Therapeutics, Inc., or Verve, a company focused on gene editing for cardiovascular disease treatments.
We can give no assurance that we will be able to secure such additional sources of capital to support our operations, or, if such capital is available to us, that such additional capital will be sufficient to meet our needs for the short or long term. 114 Revenue recognition In April 2019, we entered into a collaboration and license agreement, or the Verve Agreement, with Verve Therapeutics, Inc., or Verve, a company focused on gene editing for cardiovascular disease treatments.
These amounts are contingent upon the occurrence of future events and the timing and likelihood of such potential obligations are not known with certainty.
Milestone payments are payable at our sole discretion in cash or in shares of our common stock (valued using a volume-weighted average price). These payments are contingent upon the occurrence of future events and the timing and likelihood of such potential obligations are not known with certainty.
Comparison of the years ended December 31, 2024 and 2023 The following table summarizes our results of operations (in thousands): Years Ended December 31, 2024 2023 Change License and collaboration revenue $ 63,518 $ 377,709 $ (314,191 ) Operating expenses: Research and development 367,561 437,381 (69,820 ) General and administrative 111,525 116,813 (5,288 ) Total operating expenses 479,086 554,194 (75,108 ) Loss from operations (415,568 ) (176,485 ) (239,083 ) Other income (expense): — Change in fair value of derivative liabilities 2,272 7,500 (5,228 ) Change in fair value of non-controlling equity investments (14,093 ) (18,592 ) 4,499 Change in fair value of contingent consideration liabilities 1,592 9,740 (8,148 ) Interest and other income (expense), net 49,094 46,676 2,418 Total other income (expense) 38,865 45,324 (6,459 ) Net loss before income taxes (376,703 ) (131,161 ) (245,542 ) Provision for income taxes (39 ) (1,366 ) 1,327 Net loss $ (376,742 ) $ (132,527 ) $ (244,215 ) License and collaboration revenue License and collaboration revenue was approximately $63.5 million for the year ended December 31, 2024, compared to approximately $377.7 million for the year ended December 31, 2023, a decrease of $314.2 million.
Comparison of the years ended December 31, 2025 and 2024 The following table summarizes our results of operations (in thousands): Year Ended December 31, 2025 2024 Change License and collaboration revenue $ 139,743 $ 63,518 $ 76,225 Operating expenses: Research and development 409,618 367,561 42,057 General and administrative 113,818 111,525 2,293 Total operating expenses 523,436 479,086 44,350 Loss from operations (383,693 ) (415,568 ) 31,875 Other income (expense): Change in fair value of derivative liabilities 700 2,272 (1,572 ) Change in fair value of non-controlling equity investments 3,942 (14,093 ) 18,035 Change in fair value of contingent consideration liabilities 180 1,592 (1,412 ) Gain on sale of equity method investment 255,146 — 255,146 Interest and other income (expense), net 43,733 49,094 (5,361 ) Total other income (expense) 303,701 38,865 264,836 Net loss before income taxes (79,992 ) (376,703 ) 296,711 Provision for income taxes — (39 ) 39 Net loss $ (79,992 ) $ (376,742 ) $ 296,750 116 License and collaboration revenue License and collaboration revenue was approximately $139.7 million for the year ended December 31, 2025, compared to approximately $63.5 million for the year ended December 31, 2024, an increase of $76.2 million.
We can give no assurances that we will be able to secure such additional sources of capital to support our operations, or, if such funds are available to us, that such additional financing will be sufficient to meet our needs. 117 Cash flows The following table summarizes our sources and uses of cash (in thousands): Years Ended December 31, 2024 2023 Net cash provided by (used in) operating activities $ (347,246 ) $ (149,195 ) Net cash provided by (used in) investing activities 185,007 71,840 Net cash provided by (used in) financing activities 7,736 276,448 Net change in cash, cash equivalents and restricted cash $ (154,503 ) $ 199,093 Operating activities Net cash used in operating activities for the year ended December 31, 2024 was $347.2 million, including our net loss of $376.7 million, decreases in accrued expenses and other liabilities of $57.7 million, deferred revenue of $36.5 million and operating lease liabilities of $13.0 million, and an increase in prepaid expenses and other current assets of $5.4 million.
Cash flows The following table summarizes our sources and uses of cash (in thousands): Year Ended December 31, 2025 2024 Net cash provided by (used in) operating activities $ (345,102 ) $ (347,246 ) Net cash provided by (used in) investing activities (121,438 ) 185,007 Net cash provided by (used in) financing activities 478,049 7,736 Net change in cash, cash equivalents and restricted cash $ 11,509 $ (154,503 ) Operating activities Net cash used in operating activities for the year ended December 31, 2025 was $345.1 million, including our net loss of $80.0 million, decreases in deferred revenue of $135.4 million, operating lease liabilities of $13.5 million and other long-term liabilities of $0.3 million.
These sources of cash were offset in part by our net loss of $132.5 million, a decrease in deferred revenue of $159.6 million, a decrease in operating lease liabilities of $10.2 million, decreases in accounts payable of $7.6 million, other long-term liabilities of $0.2 million, increases in prepaid expenses and other current assets of $6.5 million and collaborations receivables of $0.1 million, as well as noncash items including amortization of investment discounts and premiums of $29.7 million, decreases in the fair value of derivative liabilities of $7.5 million and a change in the fair value of contingent consideration liabilities of $9.7 million.
These uses of cash were partially offset by increases in other liabilities of $7.7 million and accounts payable of $6.0 million, a decrease in prepaid expenses and other current assets of $4.5 million, as well as noncash items, including stock-based compensation expense of $94.2 million, depreciation and amortization expense of $22.3 million, a decrease in operating lease right-of-use, or ROU, assets of $10.4 million and a realized loss of $0.4 million on our sale of marketable securities.
We elected to make each payment in shares of our common stock and issued 174,825 shares of our common stock to each of Harvard and Broad Institute to settle these liabilities in June 2021. The remaining success payment obligations are still outstanding as of December 31, 2024.
Success payment obligations under the Harvard License Agreement and Broad License Agreement are still outstanding as of December 31, 2025. We may owe Harvard and Broad Institute success payments of up to an additional $90.0 million each, which is payable at our election in cash or shares of our common stock.
The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense.
We base our expenses related to preclinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple vendors that conduct and manage preclinical 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.
The trial will evaluate the safety, pharmacodynamics, pharmacokinetics and efficacy of BEAM-302 initially in patients with AATD-associated lung disease. The study design includes a dose exploration portion followed by a dose expansion portion to identify the optimal dose to take forward in a pivotal study.
The trial will evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy of BEAM-302. Part A of the trial is designed to evaluate AATD patients with lung disease, and Part B will evaluate AATD patients with mild to moderate liver disease with or without lung disease.
We continue to progress enrollment and global site activation and expect to report initial clinical data from multiple cohorts in the trial in the first half of 2025.
We expect to report initial data from the trial in 2026.
The decrease was partially offset by the following: • An increase of $6.3 million in stock-based compensation from additional stock options and restricted stock units granted during the year; and • An increase of $5.9 million in personnel related costs due to an increase in the number of general and administrative employees between December 31, 2023 and December 31, 2024, and increases in salaries and bonuses to existing employees. 116 Change in fair value of derivative liabilities During the year ended December 31, 2024, we recorded $2.3 million of other income related to the change in fair value of the derivative liabilities as compared to $7.5 million for the year ended December 31, 2023, driven primarily by the decline in the price of our common stock.
Change in fair value of derivative liabilities During the year ended December 31, 2025, we recorded $0.7 million of other income related to the change in fair value of derivative liabilities as compared to $2.3 million for the year ended December 31, 2024, driven primarily by a declining interest rate enviornment.
Net cash used in operating activities for the year ended December 31, 2023 was $149.2 million, including $216.4 million of cash received under the Lilly transaction, increases in accrued expenses and other liabilities of $67.7 million, as well as noncash items consisting of stock-based compensation expense of $98.6 million, a decrease in the fair value of non-controlling equity investments of $18.6 million, depreciation and amortization expense of $20.0 million and changes in operating lease ROU assets of $9.5 million.
Net cash used in operating activities for the year ended December 31, 2024 was $347.2 million, including our net loss of $376.7 million, decreases in accrued expenses and other liabilities of $57.7 million, deferred revenue of $36.5 million and operating lease liabilities of $13.0 million, and an increase in prepaid expenses and other current assets of $5.4 million.
The decrease was partially offset by the following: • An increase of $15.7 million in stock-based compensation from additional stock options and restricted stock units granted during the year; and • An increase of $4.0 million of facility and information technology, or IT, related costs, including depreciation and the expense allocated to research and development related to our leased facilities.
The increase was partially offset by the following: 117 • A decrease of $9.0 million in stock-based compensation driven by additional stock awards granted to employees in 2024; and • A decrease of $0.9 million in other expenses.
Removed
We are pursuing a long-term, staged development strategy for our base editing approach to treat hematological diseases that consists of advancing our lead ex vivo program, BEAM-101, in Wave 1, improving patient conditioning regimens in Wave 2, and enabling in vivo base editing with delivery directly into HSCs of patients via lipid nanoparticles, or LNPs, in Wave 3.
Added
Risto-cel aims to alleviate the effects of sickle cell disease by increasing HbF, which is expected to increase functional hemoglobin production and, in the case of sickle cell disease, inhibit hemoglobins S, or HbS, polymerization.
Removed
The adult enrollment target for BEACON has been achieved, and the first adolescent patients have cleared screening and enrolled in the trial. We expect to dose 30 patients in the BEACON trial by mid-2025. We also plan to present updated data from the trial in mid-2025.
Added
Food and Drug Administration, or the FDA, has granted orphan drug designation and regenerative medicine advanced therapy designation to risto-cel. Risto-cel has also been accepted into the FDA’s Chemistry, Manufacturing, and Controls Development and Readiness pilot program. In December 2025, we presented updated data from the BEACON trial at the American Society of Hematology 2025 Annual Meeting, or ASH.
Removed
Wave 2: Non-genotoxic Conditioning In parallel with Wave 1 development, we also aim to improve the transplant conditioning regimen for patients undergoing HSCT, thereby reducing toxicity challenges associated with HSCT.
Added
The presentation contained preliminary data as of August 6, 2025, from 31 patients in the trial, with follow up ranging from 0.3 to 20.4 months. The presentation data included the following: • Patients achieved mean HbF levels above 60% and a mean durable reduction in corresponding HbS below 40%.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeItem 7A. Quantitative and Qualitati ve Disclosures About Market Risk. We are exposed to market risk related to changes in interest rates. As of December 31, 2024, we had cash, cash equivalents and marketable securities of $850.7 million, which consisted of cash, money market funds, commercial paper, corporate notes and corporate equity securities.
Biggest changeItem 7A. Quantitative and Qualitati ve Disclosures About Market Risk. We are exposed to market risk related to changes in interest rates. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $1.2 billion, which consisted of cash, money market funds, commercial paper, corporate notes and corporate equity securities.

Other BEAM 10-K year-over-year comparisons