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What changed in PROTHENA CORP PUBLIC LTD CO's 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of PROTHENA CORP PUBLIC LTD CO'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.

+322 added−414 removedSource: 10-K (2026-02-27) vs 10-K (2025-02-27)

Top changes in PROTHENA CORP PUBLIC LTD CO's 2025 10-K

322 paragraphs added · 414 removed · 252 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

93 edited+47 added−113 removed154 unchanged
Biggest changePrasinezumab for the Potential Treatment of Parkinson’s Disease and Other Synucleinopathies Prasinezumab is an investigational humanized monoclonal antibody that targets alpha-synuclein, a protein found in neurons that can aggregate and spread from cell to cell, resulting in the neuronal dysfunction and loss that causes Parkinson’s disease and other synucleinopathies. Prasinezumab is the focus of our worldwide collaboration with Roche.
Biggest changeWe believe a diverse portfolio positions us to make an impact on a broad spectrum of diseases and we may also pursue opportunities in other modalities such as gene and cell therapies. 4 The following table summarizes the status of our research and development pipeline: Prasinezumab for the Potential Treatment of Parkinson’s Disease and Other Synucleinopathies Prasinezumab is an investigational humanized monoclonal antibody that targets alpha-synuclein, a protein found in neurons that can aggregate and spread from cell to cell, resulting in the neuronal dysfunction and loss that causes Parkinson’s disease and other synucleinopathies.
Failure to timely, accurately, and completely submit the required information for all payments, transfers of value and ownership or investment interests may result in civil monetary penalties; • The U.S. federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) which imposes criminal and civil liability for, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit 19 program, including any third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statements or representations, or making false statements relating to healthcare benefits, items or services.
Failure to timely, accurately, and completely submit the required information for all payments, transfers of value and ownership or investment interests may result in civil monetary penalties; • The U.S. federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) which imposes criminal and civil liability for, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program, including any third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statements or representations, or making false statements relating to healthcare benefits, items or services.
Violations of the federal Anti-Kickback Statute can result in significant civil monetary penalties and criminal fines, as well as imprisonment and exclusion from participation in government healthcare programs; • The U.S. federal civil False Claims Act, or the FCA, which may be enforced through civil whistleblower or qui tam actions and imposes significant civil penalties, treble damages and potential exclusion from government healthcare programs against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or for making a false record or statement material to an obligation to pay the federal government or for knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the federal government.
Violations of the federal Anti-Kickback Statute can result in significant civil monetary penalties and criminal fines, as well as imprisonment and exclusion from participation in government healthcare programs; 17 • The U.S. federal civil False Claims Act, or the FCA, which may be enforced through civil whistleblower or qui tam actions and imposes significant civil penalties, treble damages and potential exclusion from government healthcare programs against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or for making a false record or statement material to an obligation to pay the federal government or for knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the federal government.
In PASADENA, prasinezumab significantly reduced decline in motor function by 35% (pooled dose levels) vs. placebo after one year of treatment on the centrally rated assessment of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, a clinical examination of motor function. Motor symptoms associated with Parkinson’s disease include slowness of movement (bradykinesia), tremor, rigidity, and gait.
In PASADENA, prasinezumab significantly reduced decline in motor function by 35% (pooled dose levels) vs. placebo after 6 one year of treatment on the centrally rated assessment of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, a clinical examination of motor function. Motor symptoms associated with Parkinson’s disease include slowness of movement (bradykinesia), tremor, rigidity, and gait.
In addition to our clinical development pipeline, we have recently received clearance by the FDA for an investigational new drug (IND) application for PRX123. PRX123 is our Alzheimer’s disease vaccine program and was also granted Fast Track designation from the FDA. We also have a number of discovery- and late-preclinical-stage programs targeting proteins implicated in neurological diseases.
In addition to our clinical development pipeline, we have received clearance by the FDA for an investigational new drug (IND) application for PRX123. PRX123 is our Alzheimer’s disease vaccine program and was also granted Fast Track designation from the FDA. We also have a number of discovery- and late-preclinical-stage programs targeting proteins implicated in neurological diseases.
Prasinezumab showed potential clinical effect in the primary endpoint of time to confirmed motor progression, as assessed by ≥5 point increase in Movement Disorder Society – Unified Parkinson’s Disease 6 Rating Scale (“MDS-UPDRS”) Part III score from baseline, with a HR=0.84 [0.69-1.01] and p=0.0657.
Prasinezumab showed potential clinical effect in the primary endpoint of time to confirmed motor progression, as assessed by ≥5 point increase in Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (“MDS-UPDRS”) Part III score from baseline, with a HR=0.84 [0.69-1.01] and p=0.0657.
Failure to comply with domestic or non-domestic laws could result in various adverse consequences, including possible delay in approval or refusal to approve a product, recalls, seizures, withdrawal of an approved product from the market, the imposition of civil or criminal sanctions and the prosecution of executives overseeing our international operations. Orphan Drugs Under the U.S.
Failure to comply with domestic or non-domestic laws could result in various adverse consequences, including possible delay in approval or refusal to approve a product, recalls, seizures, withdrawal of an approved product from the market, the imposition of civil or criminal sanctions and the prosecution of executives overseeing our international operations. 16 Orphan Drugs Under the U.S.
Furthermore, BMS-986446 exposure in cerebrospinal fluid (“CSF”) was measured in the high dose cohort and based on the robust exposure of BMS-986446 in the CSF (day 29 CSF:Plasma ratio=0.2%), substantial target engagement is expected in the CNS. BMS-986446 had a desirable immunogenicity profile with no persistent BMS-986446-induced antidrug antibodies (“ADA”s) observed.
Furthermore, BMS-986446 exposure in cerebrospinal fluid (“CSF”) was measured in the high dose cohort and based 10 on the robust exposure of BMS-986446 in the CSF (day 29 CSF:Plasma ratio=0.2%), substantial target engagement is expected in the CNS. BMS-986446 had a desirable immunogenicity profile with no persistent BMS-986446-induced antidrug antibodies (“ADA”s) observed.
You can also obtain copies of these documents free of charge by writing or telephoning us at: Prothena Corporation plc, 77 Sir John Rogerson’s Quay, Block C, Grand Canal Docklands, Dublin 2, D02 VK60, Ireland, +353-1-236-2500, or through the Investors page of our website. 23
You can also obtain copies of these documents free of charge by writing or telephoning us at: Prothena Corporation plc, 77 Sir John Rogerson’s Quay, Block C, Grand Canal Docklands, Dublin 2, D02 VK60, Ireland, +353-1-236-2500, or through the Investors page of our website.
Our robust discovery engine generates new targets and compounds that have the potential to treat unmet medical needs. For investigational therapeutic programs targeting broad patient populations that may require large clinical trials and development investment, we may seek to collaborate or license these programs to pharmaceutical or biotechnology companies for development and/or commercialization.
Our robust discovery engine generates new targets and compounds that have the potential to treat unmet medical needs. For investigational therapeutic programs targeting broad patient populations that may require large clinical trials and 3 development investment, we may seek to collaborate or license these programs to pharmaceutical or biotechnology companies for development and/or commercialization.
In July 2017, we announced that the first patient had been enrolled in PASADENA, a global Phase 2 clinical trial of prasinezumab in patients with early Parkinson’s disease. The start of PASADENA triggered a $30.0 million milestone payment from Roche to Prothena, which was earned in the second quarter of 2017.
In July 2017, we announced that the first patient had been enrolled in PASADENA, a global Phase 2 clinical trial of prasinezumab in patients with early Parkinson’s disease. The start of 7 PASADENA triggered a $30.0 million milestone payment from Roche to Prothena, which was earned in the second quarter of 2017.
In May 2024, we entered into an exclusive global license agreement for PRX019 and we received an associated option exercise fee of $80.0 million. We are eligible to receive development, regulatory, and sales milestone payments of up to $617.5 million as well as tiered royalties on annual, worldwide net sales.
In May 2024, we entered into an exclusive global license agreement for PRX019 and we received an associated option exercise fee of $80 million. We are eligible to receive development, regulatory, and sales milestone payments of up to $617.5 million as well as tiered royalties on annual, worldwide net sales.
If we successfully discover, develop and commercialize any products, the launch of competitive products, including generic or biosimilar versions of any such products, may have a material adverse effect on our revenues and results of operations. Our competitive position depends in part upon our ability to discover and develop innovative and cost-effective new products.
If we successfully discover, develop and commercialize any products, the launch of 19 competitive products, including generic or biosimilar versions of any such products, may have a material adverse effect on our revenues and results of operations. Our competitive position depends in part upon our ability to discover and develop innovative and cost-effective new products.
Intellectual Property We seek to protect our proprietary technology and other intellectual property that we believe is important to our business, including by seeking, maintaining and defending patents. We also rely on trade secrets and know-how to protect our business. We may seek licenses from others as appropriate to enhance or maintain our competitive position.
Intellectual Property We seek to protect our proprietary technology and other intellectual property that we believe is important to our business, including by seeking, maintaining and defending patents. We also rely on trade secrets, know-how, and trademarks to protect our business. We may seek licenses from others as appropriate to enhance or maintain our competitive position.
BMS, with whom we are collaborating on development of BMS-986446, is responsible for manufacturing clinical supplies for any subsequent clinical trials for BMS-986446. We are dependent on BMS, and its third-party manufacturers if applicable, to manufacture these clinical supplies. 22 PRX019 - Lonza Ltd (“Lonza”) is our third-party manufacturer for drug substance and drug product for our drug candidate PRX019.
BMS, with whom we are collaborating on development of BMS-986446, is responsible for manufacturing clinical supplies for any subsequent clinical trials for BMS-986446. We are dependent on BMS, and its third-party manufacturers if applicable, to manufacture these clinical supplies. PRX019 - Lonza Ltd (“Lonza”) is our third-party manufacturer for drug substance and drug product for our drug candidate PRX019.
PRX012 for the Potential Treatment of Alzheimer’s Disease PRX012 is an investigational antibody that targets Aβ, or amyloid beta, a protein implicated in Alzheimer’s disease. Our scientists have advanced the understanding of the biology of Alzheimer’s disease and made particularly impactful and fundamental discoveries that elucidated the role amyloid plays in the disease.
PRX012 and PRX012-TfR for the Potential Treatment of Alzheimer’s Disease PRX012 is an investigational antibody that targets Aβ, or amyloid beta, a protein implicated in Alzheimer’s disease. Our scientists have advanced the understanding of the biology of Alzheimer’s disease and made particularly impactful and fundamental discoveries that elucidated the role amyloid plays in the disease.
As a result of decades of our own investigation augmented by the work of others have elucidated that targeting the appropriate epitope, with the optimal binding strength (affinity) in the context of the right clinical design with appropriate endpoints in the right patient population, can result in meaningful clinical benefit.
As a result of decades of our own investigation augmented by the work of others have elucidated that targeting the appropriate epitope, with the optimal binding strength (affinity) in the context of the right clinical design with appropriate 2 endpoints in the right patient population, can result in meaningful clinical benefit.
In addition, administrative remedies can involve requests to recall violative products, the refusal of the government to enter into supply contracts; or the refusal to approve pending 12 applications for product approvals until manufacturing or other alleged deficiencies are brought into compliance.
In addition, administrative remedies can involve requests to recall violative products, the refusal of the government to enter into supply contracts; or the refusal to approve pending applications for product approvals until manufacturing or other alleged deficiencies are brought into compliance.
Improving survival for these patients is an area of urgent need which directly aligns with birtamimab and coramitug’s differentiated depleter mechanism that targets the amyloid that causes organ dysfunction and failure and puts patients at risk for early mortality.
Improving survival for these patients is an area of urgent need which directly aligns with coramitug’s differentiated depleter mechanism that targets the amyloid that causes organ dysfunction and failure and puts patients at risk for early mortality.
In addition to the $ $30.0 million upfront payment and clinical milestone payment of $15.0 million (both in 2014), the clinical milestone payment of $30.0 million in 2017, and the clinical milestone payment of $60.0 million in 2021, Roche is also obligated to pay: 8 • up to $290.0 million upon the achievement of additional development, regulatory and various first commercial sales milestones; • up to $155.0 million upon the achievement of U.S. commercial sales milestones; • up to $175.0 million upon achievement of ex-U.S. commercial sales milestones; and • tiered, high single-digit to high double-digit royalties in the teens based on U.S. and ex-U.S. annual net sales, subject to certain adjustments, with respect to the applicable Licensed Product.
In addition to the $30.0 million upfront payment and clinical milestone payment of $15.0 million (both in 2014), the clinical milestone payment of $30.0 million in 2017, and the clinical milestone payment of $60.0 million in 2021, Roche is also obligated to pay: • up to $290.0 million upon the achievement of development, regulatory, and various first commercial sales milestones; • up to $155.0 million upon achievement of U.S. commercial sales milestones; • up to $175.0 million upon achievement of ex-U.S. commercial sales milestones; and • tiered, high single-digit to high double-digit royalties in the teens based on U.S. and ex-U.S. annual net sales, subject to certain adjustments, with respect to the applicable Licensed Product.
The application includes all relevant data available from nonclinical and clinical trials, together with detailed information relating to the product’s chemistry, manufacturing, controls and proposed labeling, among other required information.
The application includes all relevant data available from nonclinical and clinical trials, together with detailed information relating to the product’s chemistry, manufacturing, controls and proposed labeling, among other required 15 information.
The marketing application is similar to the BLA submitted to the FDA in the U.S. and is evaluated by the Committee for Medicinal Products for Human Use (the 15 “CHMP”), the expert scientific committee of the EMA.
The marketing application is similar to the BLA submitted to the FDA in the U.S. and is evaluated by the Committee for Medicinal Products for Human Use (the “CHMP”), the expert scientific committee of the EMA.
We engage and collaborate with consultants and advisors with certain scientific, clinical or other functional and/or disease area expertise to 3 help us execute specific activities related to our programs.
We engage and collaborate with consultants and advisors with certain scientific, clinical or other functional and/or disease area expertise to help us execute specific activities related to our programs.
We focus on the development of therapies for serious and/or life-threatening diseases that currently lack effective therapies or in areas where current therapies have known limitations. Our efforts in AL amyloidosis, ATTR amyloidosis, Parkinson’s disease, Alzheimer’s disease, and other neurological or peripheral amyloid diseases are examples of this.
We focus on the development of therapies for serious and/or life-threatening diseases that currently lack effective therapies or in areas where current therapies have known limitations. Our efforts in Parkinson’s disease, ATTR amyloidosis, Alzheimer’s disease, ALS and other neurological or peripheral amyloid diseases are examples of this.
Clinical Development Program for Prasinezumab Phase 2b PADOVA Clinical Trial In December 2024, topline results were announced from the Phase 2b clinical trial (PADOVA) conducted by partner Roche investigating prasinezumab in 586 people with early-stage Parkinson’s disease, treated for a minimum of 18 months while on stable symptomatic treatment.
Phase 2b PADOVA Clinical Trial In December 2024, topline results were announced from the Phase 2b clinical trial (PADOVA) conducted by partner Roche investigating prasinezumab in 586 people with early-stage Parkinson’s disease, treated for a minimum of 18 months while on stable symptomatic treatment.
If promising, we expect to advance our discovery programs into preclinical development. New target discovery will focus on areas where we can bring potential new therapies to patients expeditiously through our internal expertise and resources. Existing late discovery-stage or preclinical-stage programs may be partnered or out-licensed.
If promising, we expect to advance our discovery and preclinical programs to clinical development. New target discovery will focus on areas where we can bring potential new therapies to patients expeditiously through our internal expertise and resources. Existing late discovery-stage or preclinical-stage programs may be partnered or out-licensed.
MDS- 7 UPDRS Part III is a clinical examination of motor function that assesses motor symptoms associated with Parkinson’s disease.
MDS-UPDRS Part III is a clinical examination of motor function that assesses motor symptoms associated with Parkinson’s disease.
Once the BLA submission has been accepted for filing, the FDA’s goal is to review applications within ten months from the 60 day filing date for Standard Review (for a total of twelve months) or, in the case of Priority Review, six months from the 60 day-filing date (for a total of eight months).
Once the BLA submission has been accepted for filing, the FDA’s goal is to review applications within ten months from the 60 day filing date for Standard Review (for a total of twelve months) or, in the case of Priority Review, six months from the 60 day-filing date (for a total of eight months). European Union .
The process required by the FDA before biologic product candidates may be marketed in the U.S. generally involves, and is not limited to, the following: • completion of extensive nonclinical laboratory tests and animal studies, performed in accordance with the FDA’s Good Laboratory Practice (“GLP”) regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin and must be updated annually; • performance of adequate and well-controlled human clinical trials to establish the efficacy and safety of the product for each proposed indication, all performed in accordance with FDA’s current good clinical practices (“cGCP”) requirements; • completion of chemistry, manufacturing and control (“CMC”) processes and procedures to establish the safety and quality of the product in accordance with FDA’s current good manufacturing practices (“cGMP”) regulations; • submission to the FDA of a Biological License Application (“BLA”) for a new biologic, after completion of all required clinical trials; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities at which the product is produced and tested to assess compliance with regulatory requirements, including cGMP regulations; • referral of the BLA to an advisory committee for review, if deemed necessary; and • FDA review and approval of a BLA for a new biologic, prior to any commercial marketing or sale of the product in the U.S.
The process required by the FDA before biologic product candidates may be marketed in the U.S. generally involves, and is not limited to, the following: • completion of extensive nonclinical laboratory tests and animal studies, performed in accordance with the FDA’s Good Laboratory Practice (“GLP”) regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin and must be updated annually; • performance of adequate and well-controlled human clinical trials to establish the efficacy and safety of the product for each proposed indication, all performed in accordance with FDA’s current good clinical practices (“cGCP”) requirements; • completion of chemistry, manufacturing and control (“CMC”) processes and procedures to establish the safety and quality of the product in accordance with FDA’s current good manufacturing practices (“cGMP”) regulations; • submission to the FDA of a Biological License Application (“BLA”) for a new biologic, after completion of all required clinical trials; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities at which the product is produced and tested to assess compliance with regulatory requirements, including cGMP regulations; • referral of the BLA to an advisory committee for review, if deemed necessary; and • FDA review and approval of a BLA for a new biologic, prior to any commercial marketing or sale of the product in the U.S. 14 Nonclinical tests assess the potential safety and pharmacologic effects of a product candidate in in vitro and/or in vivo studies.
Data from company-sponsored clinical trials intended to test the efficacy and safety of a proposed use of a product, and/or from alternative sources, including studies initiated by investigators may be included in a BLA.
Data from company-sponsored clinical trials intended to support the efficacy and safety of a proposed use of a product, and/or from alternative sources, including studies initiated by investigators may be included in a BLA.
Our executive team, including employees at or above the vice president level, includes approximately 44% women, and approximately 26% who are racially or ethnically diverse. These figures were estimated by our human resources department. The well-being, health, and safety of our employees are integral to the success of our business.
Our executive team, including employees at or above the vice president level, includes approximately 39% women, and approximately 26% who are racially or ethnically diverse. These figures were estimated by our human resources department. 20 The well-being, health, and safety of our employees are integral to the success of our business.
ITEM 1. BUSINESS Overview Prothena Corporation plc (“Prothena” or the “Company”) is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases.
ITEM 1. BUSINESS Overview Prothena Corporation plc (“Prothena” or the “Company”) is a late-stage clinical biotechnology company with expertise in protein dysregulation with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases.
In November 2024, we announced that we had initiated a Phase 1 first-in-human clinical trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of single ascending and multiple doses in healthy adults. Our Discovery and Preclinical Programs We are also advancing several discovery and preclinical-stage programs for neurological diseases with significant unmet medical needs.
In November 2024, we announced that we had initiated a Phase 1 first-in-human clinical trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of single ascending and multiple doses in healthy adults. Early-Stage Programs We are also advancing several early-stage programs for neurological diseases with significant unmet medical needs.
Failure to comply with these laws can result in the imposition of significant civil and criminal penalties; • U.S. state laws that require the reporting of certain pricing information, including information pertaining to and justifying price increases, prohibit prescription drug price gouging; or impose payment caps on certain pharmaceutical products deemed by the state to be “high cost”; and • Analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, and some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.
Failure to comply with these laws can result in the imposition of significant civil and criminal penalties; • U.S. state laws that require the reporting of certain pricing information, including information pertaining to and justifying price increases, prohibit prescription drug price gouging; or impose payment caps on certain pharmaceutical products deemed by the state to be “high cost”; and • Analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, and some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures. 18 Efforts to ensure that our business arrangements will comply with applicable healthcare laws and regulations will involve substantial costs.
Our principal competitors consist of major international companies, all of which are larger and have greater financial resources, technical staff, manufacturing, R&D and marketing capabilities than we have. We also compete with smaller research companies and generic drug and biosimilar manufacturers. The degree of competition varies for each of our programs.
Competition The pharmaceutical industry is highly competitive. Our principal competitors consist of major international companies, all of which are larger and have greater financial resources, technical staff, manufacturing, R&D and marketing capabilities than we have. We also compete with smaller research companies and generic drug and biosimilar manufacturers. The degree of competition varies for each of our programs.
In July 2021, we entered into an exclusive US license agreement for BMS-986446 and we received an associated option exercise fee of $80 million.
License, Development, and Commercialization Agreement with BMS In July 2021, we entered into an exclusive US license agreement for BMS-986446 and we received an associated option exercise fee of $80 million.
Our Research and Development Pipeline Our clinical research and development pipeline includes six therapeutic antibody programs currently in clinical development: birtamimab for the potential treatment of AL amyloidosis; prasinezumab, in collaboration with Roche, for the potential treatment of Parkinson’s disease and other related synucleinopathies; coramitug, which is being developed by Novo Nordisk, for the potential treatment of ATTR amyloidosis; PRX012 for the potential treatment of Alzheimer’s disease; and BMS-986446 and PRX019, in collaboration with BMS, for the potential treatment of Alzheimer’s disease and neurodegenerative diseases respectively.
Our Research and Development Pipeline Our active clinical research and development pipeline includes four therapeutic antibody programs currently in active clinical development: prasinezumab, in collaboration with Roche, for the potential treatment of Parkinson’s disease and other related synucleinopathies; coramitug, which is being developed by Novo Nordisk, for the potential treatment of ATTR amyloidosis; and BMS-986446 and PRX019, in collaboration with BMS, for the potential treatment of Alzheimer’s disease and neurodegenerative diseases respectively.
Prescription Drug Marketing Act, which, among other things, imposes various requirements in connection with the distribution of product samples to physicians. Sales, marketing and scientific/educational grant programs must comply with the U.S. Anti-Kickback Statute, the U.S. False Claims Act, and similar state laws. Pricing and rebate programs must comply with the Medicaid rebate requirements of the U.S.
The FDA also enforces the requirements of the U.S. Prescription Drug Marketing Act, which, among other things, imposes various requirements in connection with the distribution of product samples to physicians. Sales, marketing and scientific/educational grant programs must comply with the U.S. Anti-Kickback Statute, the U.S. False Claims Act, and similar state laws.
BMS-986446 (formerly PRX005) for the Potential Treatment of Alzheimer’s Disease BMS-986446 is designed to be a best-in-class anti-tau antibody that specifically binds with high affinity the R1, R2, and R3 repeats within the microtubule binding region (“MTBR”) of tau and targets both 3R and 4R tau isoforms.
We have earned approximately $100 million to date. BMS-986446 (formerly PRX005) for the Potential Treatment of Alzheimer’s Disease BMS-986446 is designed to be a best-in-class anti-tau antibody that specifically binds with high affinity the R1, R2, and R3 repeats within the microtubule binding region (“MTBR”) of tau and targets both 3R and 4R tau isoforms.
Fueled by our deep scientific expertise built over decades of research, we are advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which our ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged.
Fueled by its deep scientific expertise built over decades of research, the Company is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged.
We are dependent on Lonza to manufacture clinical supplies for our Phase 1 clinical trial. Research and Development Our research and development expenses totaled $222.5 million, $220.6 million, and $135.6 million in 2024, 2023, and 2022, respectively.
We are dependent on Lonza to manufacture clinical supplies for our Phase 1 clinical trial. Research and Development Our research and development expenses totaled $134.9 million, $222.5 million, and $220.6 million in 2025, 2024, and 2023, respectively.
We benchmark and survey the market to ensure we maintain competitive compensation and benefits programs for our employees. As of December 31, 2024 , we employed approximately 63% women and 37% men, and approximately 43% of our employees are racially or ethnically diverse.
We benchmark and survey the market to ensure we maintain competitive compensation and benefits programs for our employees. As of December 31, 2025, we employed approximately 57% women and 43% men, and approximately 42% of our employees are racially or ethnically diverse.
Key elements of our biology-directed discovery engine include: • A focus on pathophysiology-directed targeting focused on targeting proteins with the greatest effect on disease; • Expert epitope mapping with deep expertise in determining optimal epitopes to be targeted for maximal efficacy; and • Disease driven antibody engineering for therapeutics engineered to optimally eliminate pathogenic proteins while preserving normal biology.
Key elements of our biology-directed discovery engine include: • A focus on pathophysiology-directed targeting focused on targeting proteins with the greatest effect on disease; • Expert epitope mapping with deep expertise in determining optimal epitopes to be targeted for maximal efficacy; • Disease driven antibody engineering for therapeutics engineered to optimally eliminate pathogenic proteins while preserving normal biology; • Application of CYTOPE ® technology to effectively and efficiently target previously undruggable intracellular disease targets.
Efforts to ensure that our business arrangements will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future statutes, regulations, or case law interpreting applicable fraud and abuse or other healthcare laws and regulations.
It is possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future statutes, regulations, or case law interpreting applicable fraud and abuse or other healthcare laws and regulations.
In synucleinopathies, the α-synuclein protein can misfold and aggregate to form soluble aggregates and insoluble fibrils that contribute to the pathology of the disease. There is genetic evidence for a causal role of α-synuclein in Parkinson’s disease.
While the normal function of α-synuclein is not well understood, the protein normally occurs in a soluble form. In synucleinopathies, the α-synuclein protein can misfold and aggregate to form soluble aggregates and insoluble fibrils that contribute to the pathology of the disease. There is genetic evidence for a causal role of α-synuclein in Parkinson’s disease.
AL amyloidosis and ATTR amyloidosis are diseases caused by misfolded, pathogenic forms of light chain (AL) or transthyretin (ATTR) protein that deposit as amyloid in vital organs such as the heart. Current therapeutic approaches seek to reduce the production of new pathogenic AL or ATTR protein in order to slow the formation of new amyloid deposits.
ATTR amyloidosis is a disease caused by misfolded, pathogenic forms of transthyretin (ATTR) protein that deposit as amyloid in vital organs such as the heart. Current therapeutic approaches seek to reduce the production of new pathogenic ATTR protein in order to slow the formation of new amyloid deposits.
PRX012 - Catalent Pharma Solutions, LLC (“Catalent Pharma”) is our third-party manufacturer for drug substance and Sharp Sterile Manufacturing, LLC (formerly known as “Berkshire Sterile Manufacturing, LLC” and hereinafter referred to as “Sharp Sterile”) is our third-party manufacturer for drug product for our drug candidate PRX012.
BMS-986446 (formerly PRX005) - Catalent Pharma Solutions, LLC (“Catalent Pharma”) was our third-party manufacturer for drug substance and Sharp Sterile Manufacturing, LLC (formerly known as “Berkshire Sterile Manufacturing, LLC” and hereinafter referred to as “Sharp Sterile”) was our third-party manufacturer for drug product for our drug candidate BMS-986446 for our Phase 1 clinical trial.
There are currently no treatments available that target the underlying cause of the disease. Prasinezumab is designed to block the cell-to-cell transmission of the aggregated, pathogenic forms of alpha-synuclein in Parkinson's disease, thereby slowing clinical decline. The goal of our approach is to slow the progressive neurodegenerative consequences of disease, a current unmet need.
There are currently no treatments available that target the underlying cause of the disease. Prasinezumab is designed to block the cell-to-cell transmission of the aggregated, pathogenic forms of alpha-synuclein in Parkinson's disease, thereby slowing clinical decline.
Additionally, approval must also be obtained from each clinical trial site’s Institutional Review Board (“IRB”) before the trials may be initiated, and the IRB must provide oversight of the trials until completed.
Additionally, approval must also be obtained from each clinical trial site’s Institutional Review Board (“IRB”) before the trials may be initiated, and the IRB must provide oversight of the trials until completed. There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries.
Our collaboration with Roche to develop prasinezumab for the potential treatment of Parkinson’s disease and other related synucleinopathies and our global neuroscience R&D collaboration with BMS focused on three proteins implicated in the pathogenesis of several neurodegenerative diseases are examples of this, as is the acquisition of our ATTR amyloidosis business by Novo Nordisk.
Our collaboration with Roche to develop prasinezumab for the potential treatment of Parkinson’s disease and other related synucleinopathies and the acquisition of our ATTR amyloidosis business by Novo Nordisk are examples of this, as are our two global licensing deals with BMS focused on neurodegenerative diseases.
Phase 1 includes the initial introduction of an investigational product into humans. Phase 1 clinical trials are typically more closely monitored and may be conducted in patients with the target disease or condition or in healthy volunteers.
Phase 1 clinical trials are typically more closely monitored and may be conducted in patients with the target disease or condition or in healthy volunteers.
Part 1 was a randomized, double-blind, placebo-controlled, three-arm trial and enrolled 316 patients to evaluate the efficacy and safety of prasinezumab in patients over 52 weeks.
PASADENA was a two-part Phase 2 clinical trial in early Parkinson's disease patients conducted by Roche. Part 1 was a randomized, double-blind, placebo-controlled, three-arm trial and enrolled 316 patients to evaluate the efficacy and safety of prasinezumab in patients over 52 weeks.
Coramitug (formerly PRX004) for the Potential Treatment of ATTR Amyloidosis Coramitug is an investigational antibody designed to deplete amyloid associated with disease pathology in hereditary and wild type ATTR amyloidosis, without affecting the native, normal tetrameric form of the protein.
Coramitug (formerly PRX004) for the Potential Treatment of ATTR Amyloidosis Coramitug is an investigational antibody designed to deplete amyloid associated with disease pathology in hereditary and wild type ATTR amyloidosis, without affecting the native, normal tetrameric form of the protein. 8 ATTR amyloidosis is a rare, progressive and fatal disease characterized by deposition of abnormal, non-native forms of TTR protein (amyloid) in vital organs.
In many countries, the healthcare professionals we interact with may meet the definition of a government official for purposes of the FCPA.
Bribery Act) for the purpose of obtaining or retaining business abroad. In many countries, the healthcare professionals we interact with may meet the definition of a government official for purposes of the FCPA.
An IND is a request for authorization from the FDA to manufacture and administer an investigational drug or biologic product to humans. The IND includes the proposed protocol(s) and general investigational plan for human studies.
The results of these studies must be submitted to the FDA as part of an IND before human testing may proceed. An IND is a request for authorization from the FDA to manufacture and administer an investigational drug or biologic product to humans. The IND includes the proposed protocol(s) and general investigational plan for human studies.
If we fail to discover and develop new products, our business, financial condition and results of operations will be materially and adversely affected. Manufacturing Birtamimab - Boehringer Ingelheim Biopharmaceuticals GmbH (“BI”) manufactured clinical supplies of our drug candidate birtamimab for our prior Phase 1, Phase 2 (PRONTO) and Phase 3 (VITAL) clinical trials.
If we fail to discover and develop new products, our business, financial condition and results of operations will be materially and adversely affected. Manufacturing Prasinezumab - Boehringer Ingelheim Biopharmaceuticals GmbH (“BI”) manufactured clinical supplies of our drug candidate prasinezumab for our completed Phase 1a single ascending dose and Phase 1b multiple ascending dose clinical trials.
For more information, see “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” Employees and Human Capital Management As of December 31, 2024 , we had 163 employees, including 27 holding M.D. and/or Ph.D. degrees. Of our employees, 116 were engaged in research and development activities and the remainder were working in general and administrative areas.
For more information, see “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” Employees and Human Capital Management As of December 31, 2025, we had 67 employees, including 13 who held M.D. and/or Ph.D. degrees.Of our total employees, 36 were engaged in research and development (R&D) activities and the remainder were engaged in general and administrative (G&A) functions.
The protein α-synuclein is found extensively in neurons and is a major component of pathological inclusions that characterize several neurodegenerative disorders, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, which collectively are termed synucleinopathies. While the normal function of α-synuclein is not well understood, the protein normally occurs in a soluble form.
Prasinezumab is the focus of our worldwide collaboration with Roche. The protein α-synuclein is found extensively in neurons and is a major component of pathological inclusions that characterize several neurodegenerative disorders, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, which collectively are termed synucleinopathies.
Phase 2 Clinical Trial In the first quarter of 2024, BMS advanced the anti-tau program BMS-986446 with the initiation of a Phase 2 clinical trial (NCT06268886). This is a randomized, double-blind, placebo-controlled, global, Phase 2 clinical trial designed to evaluate the efficacy, safety, and tolerability of BMS-986446, an anti-MTBR tau monoclonal antibody, in approximately 475 participants with early Alzheimer's disease.
This is a randomized, double-blind, placebo-controlled, global, Phase 2 clinical trial designed to evaluate the efficacy, safety, and tolerability of BMS-986446, an anti-MTBR tau monoclonal antibody, in approximately 310 participants with early Alzheimer's disease. Participants will be randomized into one of three treatment arms including placebo, BMS-986446 Dose A, and BMS-986446 Dose B.
Coramitug has been shown in preclinical studies to inhibit amyloid fibril formation, neutralize soluble aggregate forms of non-native TTR, and promote clearance of insoluble amyloid fibrils through antibody-mediated phagocytosis.
Coramitug’s proposed mechanism of action is to deplete both circulating non-native TTR to prevent further deposition and deposited amyloid to improve organ function. Coramitug has been shown in preclinical studies to inhibit amyloid fibril formation, neutralize soluble aggregate forms of non-native TTR, and promote clearance of insoluble amyloid fibrils through antibody-mediated phagocytosis.
Current therapies do not adequately address the needs of patients with AL and ATTR amyloidosis who have advanced stages of cardiac disease due to amyloid deposition.
Coramitug is designed to target and clear amyloid deposited in organs in order to improve organ function. Current therapies do not adequately address the needs of patients with ATTR amyloidosis who have advanced stages of cardiac disease due to amyloid deposition.
However, simply reducing new pathogenic protein production may not be adequate for patients who are at high risk of early mortality due to the substantial existing amyloid deposition in their vital organs.
However, simply reducing new pathogenic protein production may not be adequate for patients who are at high risk of early mortality due to the substantial existing amyloid deposition in their vital organs. The therapeutic approach we are developing with coramitug (formerly PRX004) for ATTR amyloidosis is an investigational monoclonal antibody designed to clear the pathogenic amyloid deposits.
Roche, with whom we are collaborating on development of prasinezumab, is manufacturing clinical supplies for the ongoing Phase 2 and any subsequent clinical trials for prasinezumab. We are dependent on Roche, and its third-party manufacturers if applicable, to manufacture these clinical supplies.
Roche, with whom we are collaborating on development of prasinezumab, is manufacturing clinical supplies for any subsequent clinical trials for prasinezumab. We are dependent on Roche, and its third-party manufacturers if applicable, to manufacture these clinical supplies. Coramitug (formerly PRX004) - Rentschler Biopharma SE (“Rentschler”) manufactured clinical supplies of our drug candidate coramitug for our completed Phase 1 clinical trial.
We are eligible to receive regulatory and sales milestone payments of up to $563 million, as well as tiered royalties on annual, worldwide net sales. 10 Phase 1 Clinical Trial In this first-in-human, randomized, placebo controlled, single ascending dose (“SAD”) clinical trial, healthy volunteers (n=19) were enrolled into three BMS-986446 dose level cohorts (low, medium or high dose) and randomized in a 3:1 drug to placebo ratio.
Phase 1 Clinical Trial In this first-in-human, randomized, placebo controlled, single ascending dose (“SAD”) clinical trial, healthy volunteers (n=19) were enrolled into three BMS-986446 dose level cohorts (low, medium or high dose) and randomized in a 3:1 drug to placebo ratio.
These findings led to the development of a drug discovery and development organization that generated first-in-class clinical candidates in Alzheimer’s disease, Parkinson’s disease, and AL and ATTR amyloidosis.
Our legacy includes fundamental discoveries in the understanding of Alzheimer’s disease biology including identifying and elucidating the role Aβ plays in Alzheimer’s disease pathology. These findings led to the development of a drug discovery and development organization that generated first-in-class clinical candidates in Alzheimer’s disease, Parkinson’s disease, and ATTR amyloidosis.
We are advancing our lead candidate, PRX012, as a next-generation approach for subcutaneous administration to address the unmet need of millions of patients with presymptomatic or early symptomatic Alzheimer's disease.
PRX012 is a potential next-generation anti-Aβ antibody designed for subcutaneous administration to address the unmet need of millions of patients with presymptomatic or early symptomatic Alzheimer's disease.
In both forms of the disease, patients can experience a spectrum of clinical manifestations due to deposition of amyloid that can affect multiple organs, most commonly the heart and/or nervous system.
ATTR amyloidosis can be hereditary (hATTR) when caused by a mutation in the TTR gene, or wild-type (wtATTR) when it occurs sporadically. In both forms of the disease, patients can experience a spectrum of clinical manifestations due to deposition of amyloid that can affect multiple organs, most commonly the heart and/or nervous system.
We have employed our discovery engine to optimally target key epitopes on misfolded proteins including Aβ, tau, alpha-synuclein, light chain, and transthyretin to relevantly influence biology and achieve clinical benefit across a number of indications.
We have employed our discovery engine to optimally target key epitopes on misfolded proteins including alpha-synuclein, transthyretin, tau and Aβ to relevantly influence biology and achieve clinical benefit across a number of indications. In addition, we have applied our new CYTOPE ® technology to target phosphorylated TDP-43, a key pathogenic feature of TDP-43 proteinopathies, including amyotrophic lateral sclerosis or ALS.
In July 2023, we entered into an exclusive global license agreement for BMS-986446, which as discussed above supersedes and replaces the US license agreement in its entirety and we received an associated option exercise fee of $55 million.
In July 2023, we entered into an exclusive global license agreement for BMS-986446, which supersedes and replaces the US license agreement in its entirety and we received an associated option exercise fee of $55 million. We are eligible to receive regulatory and sales milestone payments of up to $563 million, as well as tiered royalties on annual, worldwide net sales.
There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries. 13 The clinical investigation of a pharmaceutical, including a biologic, is generally divided into three phases. Although the phases are usually conducted sequentially, they may overlap or be combined. The three phases of an investigation are as follows: • Phase 1.
The clinical investigation of a pharmaceutical, including a biologic, is generally divided into three phases. Although the phases are usually conducted sequentially, they may overlap or be combined. The three phases of an investigation are as follows: • Phase 1. Phase 1 includes the initial introduction of an investigational product into humans.
Coramitug (formerly PRX004) - Rentschler manufactured clinical supplies of our drug candidate coramitug for our completed Phase 1 clinical trial. In July 2021, we sold shares of one of our wholly-owned subsidiaries to Novo Nordisk. In connection with the transaction, Novo Nordisk acquired our ATTR amyloidosis business, including our drug candidate coramitug.
In July 2021, we sold shares of one of our wholly-owned subsidiaries to Novo Nordisk. In connection with the transaction, Novo Nordisk acquired our ATTR amyloidosis business, including our drug candidate coramitug. We are dependent on Novo Nordisk, and its third-party manufacturers if applicable, to manufacture clinical supplies of coramitug.
Bribery Act prohibit companies and their representatives from offering, promising, authorizing or making payments to governmental officials (and certain private individuals under the Irish Corruption Act and 16 the U.K. Bribery Act) for the purpose of obtaining or retaining business abroad.
Foreign Corrupt Practices Act (the “FCPA”), the Irish Criminal Justice (Corruption Offences) Act 2018 (the “Irish Corruption Act”) and the U.K. Bribery Act prohibit companies and their representatives from offering, promising, authorizing or making payments to governmental officials (and certain private individuals under the Irish Corruption Act and the U.K.
It is likely that additional state and federal healthcare reform measures will continue to be adopted in the future, which could limit the amounts that federal and state governments will pay for healthcare products and services, potentially reducing demand for a pharmaceutical manufacturer’s products or adding additional pricing pressure. 18 Other Healthcare Laws Although we currently do not have any products on the market, if our drug candidates are approved and we begin commercialization, we may be subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and other jurisdictions in which we conduct our business.
Other Healthcare Laws Although we currently do not have any products on the market, if our drug candidates are approved and we begin commercialization, we may be subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and other jurisdictions in which we conduct our business.
In the U.S., a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent.
Patent and Trademark Office in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent.
Omnibus Budget Reconciliation Act. We may also be subject to the U.S. Physician Payment Sunshine Act (the “Sunshine Act”) which regulates disclosure of payments to healthcare professionals and providers. The U.S. Foreign Corrupt Practices Act (the “FCPA”), the Irish Criminal Justice (Corruption Offences) Act 2018 (the “Irish Corruption Act”) and the U.K.
Pricing and rebate programs must comply with the Medicaid rebate requirements of the U.S. Omnibus Budget Reconciliation Act. We may also be subject to the U.S. Physician Payment Sunshine Act (the “Sunshine Act”) which regulates disclosure of payments to healthcare professionals and providers. The U.S.
Proteins that misfold and aggregate to form amyloid are associated with a multitude of common and rare human diseases that can gravely damage vital organs. Amyloid can affect any organ in the body. Our pipeline reflects our deep understanding of the contribution of these toxic proteins to the cause and progression of disease.
When this happens, proteins misfold and propagate many diseases that are not adequately addressed by current therapies. Proteins that misfold and aggregate to form amyloid are associated with a multitude of common and rare human diseases that can gravely damage vital organs. Amyloid can affect any organ in the body.
Within these types of collaborations, we will evaluate several strategic options for designing and operationalizing early to late-stage development programs. This includes evaluating the option of designing and operationalizing clinical programs ourselves or with a partner. We also consider opportunities to acquire or license rights or invest in differentiated product candidates or technologies to complement our existing R&D pipeline.
Within these types of collaborations, we will evaluate several strategic options for designing and operationalizing early to late-stage development programs. This includes evaluating the option of designing and operationalizing clinical programs ourselves or with a partner. In addition, we will leverage research collaborations with large pharmaceuticals companies to explore applications of our CYTOPE ® technology.
In January 2024, we announced that the FDA has cleared the IND application for PRX123 and granted PRX123 Fast Track designation. PRX019 for the Potential Treatment of Neurodegenerative Diseases PRX019 is an investigational antibody for the potential treatment of neurodegenerative diseases in development in collaboration with BMS. In December 2023, the FDA cleared the IND application for PRX019.
In October 2025, Bristol Myers Squibb obtained Fast Track designation from the U.S. FDA for BMS-986446 for the potential treatment of Alzheimer’s disease. PRX019 for the Potential Treatment of Neurodegenerative Diseases PRX019 is an investigational antibody for the potential treatment of neurodegenerative diseases in development in collaboration with BMS. In December 2023, the FDA cleared the IND application for PRX019.
Instead, our internally discovered pipeline has generated multiple proof points that our molecules have successfully influenced biology in a manner that translates into clinical benefit. We’ve most recently 2 demonstrated this in AL amyloidosis, ATTR amyloidosis, and Parkinson’s disease where preclinical findings in our programs have translated to positive clinical data. • Focus on diseases that lack effective therapies.
We’ve most recently demonstrated this in ATTR amyloidosis and Parkinson’s disease where preclinical findings in our programs have translated to positive clinical data leading our partners to advance our programs into Phase 3 development. • Focus on diseases that lack effective therapies.
This results in predominant symptoms of neuropathy (hATTR-PN) and/or cardiomyopathy (hATTR-CM), as well as other disease manifestations.
This results in predominant symptoms of neuropathy (hATTR-PN) and/or cardiomyopathy (hATTR-CM), as well as other disease manifestations. It is estimated that there are approximately 50,000 patients with hATTR worldwide, with approximately 10,000 characterized as hATTR-PN and 40,000 characterized as hATTR-CM.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIf Roche’s efforts are unsuccessful, our ability to generate future product sales from prasinezumab outside the United States would be significantly reduced. Under our License Agreement, outside of the U.S., Roche has responsibility for developing and commercializing prasinezumab and any future Licensed Products targeting α- synuclein.
Biggest changeOutside of the United States, we are solely dependent on the efforts and commitments of Roche, either directly or through third parties, to further develop and, if prasinezumab is approved by applicable regulatory authorities, commercialize prasinezumab. If Roche’s efforts are unsuccessful, our ability to generate future product sales from prasinezumab outside the United States would be significantly reduced.
In addition, our right to co-promote prasinezumab and other Licensed Products will terminate if we commence a Phase 3 study for a competitive product that treats Parkinson’s disease.
In addition, our right to co-promote prasinezumab and other Licensed Products will terminate if we commence a Phase 3 study for a competitive product that treats Parkinson’s disease.
Similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, among others, to track and report annually to CMS information related to “payments or other transfers of value” made to U.S.-licensed physicians (defined to include doctors, dentists, optometrists, podiatrists and licensed chiropractors), physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiology assistants, certified nurse midwives, and teaching hospitals; as well as tracking and reporting of ownership and investment interests held by the U.S.-licensed physicians (as defined by statute) and their immediate family members; • analogous state laws and regulations that may apply to sales or marketing arrangements and claims for healthcare items or services reimbursed by non-governmental third-party payers, including private insurers, that may be broader in scope than their federal equivalents; state laws and regulations that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state laws and regulations that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or require the disclosure of marketing expenditures and other pricing information; and • similar and other laws and regulations in the U.S.
Similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, among others, to track and report annually to CMS information related to “payments or other transfers of value” made to U.S.-licensed physicians (defined to include doctors, dentists, optometrists, podiatrists and licensed chiropractors), physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiology assistants, certified nurse midwives, and teaching hospitals; as well as tracking and reporting of ownership and investment interests held by the U.S.-licensed physicians (as defined by statute) and their immediate family members; • analogous state laws and regulations that may apply to sales or marketing arrangements and claims for healthcare items or services reimbursed by non-governmental third-party payers, including private insurers, that may be broader in scope than their federal equivalents; state laws and regulations that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state laws and regulations that require drug manufacturers to report information related to payments and other transfers of 38 value to physicians and other healthcare providers or require the disclosure of marketing expenditures and other pricing information; and • similar and other laws and regulations in the U.S.
Even if any of our drug candidates receives marketing approval, as greater numbers of patients use a drug following its approval, an increase in the incidence or severity of side effects or the incidence of other post-approval problems that were not seen or anticipated during pre-approval clinical trials could result in a number of potentially significant negative consequences, including: • regulatory authorities may withdraw their approval of the product; • regulatory authorities may require the addition of labeling statements, such as contraindications, warnings, or precautions; or impose additional safety monitoring or reporting requirements; • we may be required to change the way the product is administered, or to conduct additional clinical trials; 35 • we could be sued and held liable for harm caused to patients; and • our reputation may suffer.
Even if any of our drug candidates receives marketing approval, as greater numbers of patients use a drug following its approval, an increase in the incidence or severity of side effects or the incidence of other post-approval problems that were not seen or anticipated during pre-approval clinical trials could result in a number of potentially significant negative consequences, including: • regulatory authorities may withdraw their approval of the product; • regulatory authorities may require the addition of labeling statements, such as contraindications, warnings, or precautions; or impose additional safety monitoring or reporting requirements; • we may be required to change the way the product is administered, or to conduct additional clinical trials; • we could be sued and held liable for harm caused to patients; and • our reputation may suffer.
In July 2020, the Court of Justice of the EU limited how organizations could lawfully transfer personal data from the EEA to the United States by invalidating the EU-US Privacy Shield Framework for purposes of international transfers and imposing further restrictions on the use of standard contractual clauses (“EU SCCs”) including, a requirement for companies to carry out a transfer privacy impact assessment (“TIA”), which, among other things, assesses the laws governing access to personal data in the recipient 28 country and considers whether supplementary measures that provide privacy protections additional to those provided under the EU SCCs will need to be implemented to ensure an “essentially equivalent” level of data protection to that afforded in the EEA.
In July 2020, the Court of Justice of the EU limited how organizations could lawfully transfer personal data from the EEA to the United States by invalidating the EU-US Privacy Shield Framework for purposes of international transfers and imposing further restrictions on the use of standard contractual clauses (“EU SCCs”) including, a requirement for companies to carry out a transfer privacy impact assessment (“TIA”), which, among other things, assesses the laws governing access to personal data in the recipient country and considers whether supplementary measures that provide privacy protections additional to those provided under the EU SCCs will need to be implemented to ensure an “essentially equivalent” level of data protection to that afforded in the EEA.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or not previously observed in clinical trials, or problems with our third-party manufacturers or manufacturing processes, or failure to comply with the regulatory requirements of the FDA, the EMA, or other comparable regulatory authorities could subject us to administrative or judicially imposed sanctions, including: • restrictions on the marketing of our products or their manufacturing processes; • warning letters; • civil or criminal penalties; • fines; • injunctions; • product seizures or detentions; • import or export bans; • voluntary or mandatory product recalls and related publicity requirements; • suspension or withdrawal of regulatory approvals; • total or partial suspension of production; and • refusal to approve pending applications for marketing approval of new products or supplements to approved applications.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or not previously observed in clinical trials, or problems with our third-party manufacturers or manufacturing processes, or failure to comply with the regulatory requirements of the FDA, the EMA, or other comparable regulatory authorities could subject us to administrative or judicially imposed sanctions, including: • restrictions on the marketing of our products or their manufacturing processes; • warning letters; • civil or criminal penalties; • fines; 31 • injunctions; • product seizures or detentions; • import or export bans; • voluntary or mandatory product recalls and related publicity requirements; • suspension or withdrawal of regulatory approvals; • total or partial suspension of production; and • refusal to approve pending applications for marketing approval of new products or supplements to approved applications.
For example: • others may be able to make drug candidates that are similar to ours but that are not covered by the claims of the patents that we own or have exclusively licensed; • we or our licensors or future collaborators might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or have exclusively licensed; • we or our licensors or future collaborators might not have been the first to file patent applications covering certain of our inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; • it is possible that our pending patent applications will not lead to issued patents; • issued patents that we own or have exclusively licensed may be held invalid or unenforceable, as a result of legal challenges by our competitors; • 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 may not develop additional proprietary technologies that are patentable; • we cannot predict the scope of protection of any patent issuing based on our patent applications, including whether the patent applications that we own or in-license will result in issued patents with claims that cover our drug candidates or uses thereof in the United States or in other foreign countries; • the claims of any patent issuing based on our patent applications may not provide protection against competitors or any competitive advantages, or may be challenged by third parties; • if enforced, a court may not hold that our patents are valid, enforceable and infringed; • we may need to initiate litigation or administrative proceedings to enforce and/or defend our patent rights which will be costly whether we win or lose; 55 • 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; • we may fail to adequately protect and police our trademarks and trade secrets; and • the patents of others may have an adverse effect on our business, including if others obtain patents claiming subject matter similar to or improving that covered by our patents and patent applications.
For example: • others may be able to make drug candidates that are similar to ours but that are not covered by the claims of the patents that we own or have exclusively licensed; • we or our licensors or future collaborators might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or have exclusively licensed; • we or our licensors or future collaborators might not have been the first to file patent applications covering certain of our inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; • it is possible that our pending patent applications will not lead to issued patents; • issued patents that we own or have exclusively licensed may be held invalid or unenforceable, as a result of legal challenges by our competitors; • 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 may not develop additional proprietary technologies that are patentable; • we cannot predict the scope of protection of any patent issuing based on our patent applications, including whether the patent applications that we own or in-license will result in issued patents with claims that cover our drug candidates or uses thereof in the United States or in other foreign countries; • the claims of any patent issuing based on our patent applications may not provide protection against competitors or any competitive advantages, or may be challenged by third parties; • if enforced, a court may not hold that our patents are valid, enforceable and infringed; • we may need to initiate litigation or administrative proceedings to enforce and/or defend our patent rights which will be costly whether we win or lose; 50 • 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; • we may fail to adequately protect and police our trademarks and trade secrets; and • the patents of others may have an adverse effect on our business, including if others obtain patents claiming subject matter similar to or improving that covered by our patents and patent applications.
The market price of our ordinary shares may fluctuate widely, depending upon many factors, some of which may be beyond our control, including: • our ability to obtain financing as needed; • progress in and results from our ongoing or future nonclinical research and clinical trials; • the execution of our agreements with third parties, including with Roche, BMS, and Novo Nordisk; • failure or delays in advancing our nonclinical drug candidates or other drug candidates we may develop in the future into clinical trials; • results of clinical trials conducted by others, including on drugs that would compete with our drug candidates; • issues in manufacturing our drug candidates; • regulatory developments or enforcement in the U.S. and other countries; • developments or disputes concerning patents or other proprietary rights; • introduction of technological innovations or new commercial products by our competitors; • changes in estimates or recommendations by securities analysts, if any, who cover our company; • public concern over our drug candidates; • litigation; • future sales of our ordinary shares by us or by existing shareholders; • general market conditions; • changes in the structure of healthcare payment systems; • failure of any of our drug candidates, if approved, to achieve commercial success; • economic and other external factors or other disasters or crises; • period-to-period fluctuations in our financial results; • overall fluctuations in U.S. equity markets; • our quarterly or annual results, or those of other companies in our industry; 56 • announcements by us or our competitors of significant acquisitions or dispositions; • the operating and ordinary share price performance of other comparable companies; • investor perception of our company and the drug development industry; • natural or environmental disasters that investors believe may affect us; • changes in tax laws or regulations applicable to our business or the interpretations of those tax laws and regulations by taxing authorities; or • fluctuations in the budgets of federal, state and local governmental entities around the world.
The market price of our ordinary shares may fluctuate widely, depending upon many factors, some of which may be beyond our control, including: • our ability to obtain financing as needed; • progress in and results from our ongoing or future nonclinical research and clinical trials; • the execution of our agreements with third parties, including with Roche, BMS, and Novo Nordisk; • failure or delays in advancing our nonclinical drug candidates or other drug candidates we may develop in the future into clinical trials; • results of clinical trials conducted by others, including on drugs that would compete with our drug candidates; • issues in manufacturing our drug candidates; • regulatory developments or enforcement in the U.S. and other countries; • developments or disputes concerning patents or other proprietary rights; • introduction of technological innovations or new commercial products by our competitors; • changes in estimates or recommendations by securities analysts, if any, who cover our company; • public concern over our drug candidates; • litigation; • future sales of our ordinary shares by us or by existing shareholders; • general market conditions; • changes in the structure of healthcare payment systems; • failure of any of our drug candidates, if approved, to achieve commercial success; • economic and other external factors or other disasters or crises; • period-to-period fluctuations in our financial results; • overall fluctuations in U.S. equity markets; • our quarterly or annual results, or those of other companies in our industry; 51 • announcements by us or our competitors of significant acquisitions or dispositions; • the operating and ordinary share price performance of other comparable companies; • investor perception of our company and the drug development industry; • natural or environmental disasters that investors believe may affect us; • changes in tax laws or regulations applicable to our business or the interpretations of those tax laws and regulations by taxing authorities; or • fluctuations in the budgets of federal, state and local governmental entities around the world.
Research, development, commercialization and/or strategic collaborations, including those that we have with Roche and BMS, are subject to numerous risks, which include the following: • collaborators may have significant control or discretion in determining the efforts and resources that they will apply to a collaboration, and might not commit sufficient efforts and resources or might misapply those efforts and resources; • we may have limited influence or control over the approaches to research, development, and/or commercialization of products candidates in the territories in which our collaboration partners lead research, development, and/or commercialization; • collaborators might not pursue research, development, and/or commercialization of collaboration drug candidates or might elect not to continue or renew research, development, and/or commercialization programs based on nonclinical and/or clinical trial results, changes in their strategic focus due to the acquisition of competing products, availability of funding, or other factors, such as a business combination that diverts resources or creates competing priorities; • collaborators might delay, provide insufficient resources to, or modify or stop research or clinical development for collaboration drug candidates or require a new formulation of a drug candidate for clinical testing; • collaborators could develop or acquire products outside of the collaboration that compete directly or indirectly with our drug candidates or require a new formulation of a drug candidate for nonclinical and/or clinical testing; 30 • collaborators with sales, marketing, and distribution rights to one or more drug candidates might not commit sufficient resources to sales, marketing, and distribution or might otherwise fail to successfully commercialize those drug candidates; • collaborators might not properly maintain or defend our intellectual property rights or might use our intellectual property improperly or in a way that jeopardizes our intellectual property or exposes us to potential liability; • collaboration activities might result in the collaborator having intellectual property covering our activities or drug candidates, which could limit our rights or ability to research, develop, and/or commercialize our drug candidates; • collaborators might not be in compliance with laws applicable to their activities under the collaboration, which could impact the collaboration or us; • disputes might arise between us and a collaborator that could cause a delay or termination of the collaboration or result in costly litigation that diverts management attention and resources; and • collaborations might be terminated, which could result in a need for additional capital to pursue further research, development, and/or commercialization of our drug candidates.
Research, development, commercialization and/or strategic collaborations, including those that we have with Roche and BMS, are subject to numerous risks, which include the following: • collaborators may have significant control or discretion in determining the efforts and resources that they will apply to a collaboration, and might not commit sufficient efforts and resources or might misapply those efforts and resources; 27 • we may have limited influence or control over the approaches to research, development, and/or commercialization of products candidates in the territories in which our collaboration partners lead research, development, and/or commercialization; • collaborators might not pursue research, development, and/or commercialization of collaboration drug candidates or might elect not to continue or renew research, development, and/or commercialization programs based on nonclinical and/or clinical trial results, changes in their strategic focus due to the acquisition of competing products, availability of funding, or other factors, such as a business combination that diverts resources or creates competing priorities; • collaborators might delay, provide insufficient resources to, or modify or stop research or clinical development for collaboration drug candidates or require a new formulation of a drug candidate for clinical testing; • collaborators could develop or acquire products outside of the collaboration that compete directly or indirectly with our drug candidates or require a new formulation of a drug candidate for nonclinical and/or clinical testing; • collaborators with sales, marketing, and distribution rights to one or more drug candidates might not commit sufficient resources to sales, marketing, and distribution or might otherwise fail to successfully commercialize those drug candidates; • collaborators might not properly maintain or defend our intellectual property rights or might use our intellectual property improperly or in a way that jeopardizes our intellectual property or exposes us to potential liability; • collaboration activities might result in the collaborator having intellectual property covering our activities or drug candidates, which could limit our rights or ability to research, develop, and/or commercialize our drug candidates; • collaborators might not be in compliance with laws applicable to their activities under the collaboration, which could impact the collaboration or us; • disputes might arise between us and a collaborator that could cause a delay or termination of the collaboration or result in costly litigation that diverts management attention and resources; and • collaborations might be terminated, which could result in a need for additional capital to pursue further research, development, and/or commercialization of our drug candidates.
The operational and financial impact of a business disruption beyond our control, such as a public health crisis, geopolitical turmoil, or an adverse weather event has, and could, adversely affect our business in the following ways: • As we have seen with the outbreak of the COVID-19 pandemic, outbreaks of epidemic, pandemic, or contagious disease or other public health emergencies have historically and may in the future disrupt our operations, including clinical trials, research and nonclinical studies, the manufacture or shipment of both drug substance and finished drug product for drug candidates for preclinical testing and clinical trials, and access to stable credit and financial markets in the United States and worldwide.
The operational and financial impact of a business disruption beyond our control, such as a public health crisis, geopolitical turmoil, or an adverse weather event has, and could, adversely affect our business in the following ways: 23 • As we have seen with the outbreak of the COVID-19 pandemic, outbreaks of epidemic, pandemic, or contagious disease or other public health emergencies have historically and may in the future disrupt our operations, including clinical trials, research and nonclinical studies, the manufacture or shipment of both drug substance and finished drug product for drug candidates for preclinical testing and clinical trials, and access to stable credit and financial markets in the United States and worldwide.
In addition, a clinical trial may be delayed, suspended or terminated by us, the FDA, the EMA or other comparable regulatory authorities, the IRBs for the sites where the IRBs are overseeing a trial, or the safety oversight committee overseeing the clinical trial at issue due to a number of factors, including: • failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols; • inspection of the clinical trial operations or trial sites by the FDA, the EMA, or other regulatory authorities resulting in the imposition of a clinical hold on or imposition of additional conditions for the conduct of the trial; • interpretation of data by the FDA, the EMA, or other regulatory authorities; • requirement by the FDA, the EMA, or other regulatory authorities to perform additional studies; • failure to achieve primary or secondary endpoints or other failure to demonstrate efficacy or adequate safety; • unforeseen safety issues; or • lack of adequate funding to continue the clinical trial.
In addition, a clinical trial may be delayed, suspended or terminated by us, the FDA, the EMA or other comparable regulatory authorities, the IRBs for the sites where the IRBs are overseeing a trial, or the safety oversight committee overseeing the clinical trial at issue due to a number of factors, including: • failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols; • inspection of the clinical trial operations or trial sites by the FDA, the EMA, or other regulatory authorities resulting in the imposition of a clinical hold on or imposition of additional conditions for the conduct of the trial; • interpretation of data by the FDA, the EMA, or other regulatory authorities; • requirement by the FDA, the EMA, or other regulatory authorities to perform additional studies; • failure to achieve primary or secondary endpoints or other failure to demonstrate efficacy or adequate safety; • unforeseen safety issues; or 29 • lack of adequate funding to continue the clinical trial.
These laws include: • the U.S. federal Anti-Kickback Statute, an intent-based federal criminal statute which prohibits, among other things, persons and entities from knowingly and willfully soliciting, receiving, offering, providing, or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or 42 the purchase, lease, order or arrangement for, or recommendation of an item or service for which payment may be made, in whole or in part, by a federal healthcare program, such as the Medicare and Medicaid programs.
These laws include: • the U.S. federal Anti-Kickback Statute, an intent-based federal criminal statute which prohibits, among other things, persons and entities from knowingly and willfully soliciting, receiving, offering, providing, or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or arrangement for, or recommendation of an item or service for which payment may be made, in whole or in part, by a federal healthcare program, such as the Medicare and Medicaid programs.
A number of events, including any of the following, could delay the completion of our ongoing or planned clinical trials and negatively impact our ability to obtain regulatory approval for, and to market and sell, a particular drug candidate: • conditions imposed on us by the FDA, the EMA, or other comparable regulatory authorities regarding the scope or design of our clinical trials; • delays in obtaining, or our inability to obtain, required approvals from institutional review boards (“IRBs”) or other reviewing entities at clinical sites selected for participation in our clinical trials; • insufficient supply or deficient quality of our drug candidates or other materials necessary to conduct our clinical trials; • delays in obtaining regulatory authority authorization for the conduct of our clinical trials; • lower than anticipated enrollment and/or retention rate of subjects in our clinical trials, which can be impacted by a number of factors, including size of patient population, design of trial protocol, trial length, eligibility criteria, perceived risks and benefits of the drug candidate, patient proximity to trial sites, patient referral practices of physicians, availability of other treatments for the relevant disease, and competition from other clinical trials; 31 • slower than expected rates of events in trials with a primary endpoint that is event-based; • serious and unexpected drug-related side effects experienced by subjects in clinical trials; or • failure of our third-party contractors and collaborators to meet their contractual obligations to us or otherwise meet their development or other objectives in a timely manner.
A number of events, including any of the following, could delay 28 the completion of our ongoing or planned clinical trials and negatively impact our ability to obtain regulatory approval for, and to market and sell, a particular drug candidate: • conditions imposed on us by the FDA, the EMA, or other comparable regulatory authorities regarding the scope or design of our clinical trials; • delays in obtaining, or our inability to obtain, required approvals from institutional review boards (“IRBs”) or other reviewing entities at clinical sites selected for participation in our clinical trials; • insufficient supply or deficient quality of our drug candidates or other materials necessary to conduct our clinical trials; • delays in obtaining regulatory authority authorization for the conduct of our clinical trials; • lower than anticipated enrollment and/or retention rate of subjects in our clinical trials, which can be impacted by a number of factors, including size of patient population, design of trial protocol, trial length, eligibility criteria, perceived risks and benefits of the drug candidate, patient proximity to trial sites, patient referral practices of physicians, availability of other treatments for the relevant disease, and competition from other clinical trials; • slower than expected rates of events in trials with a primary endpoint that is event-based; • serious and unexpected drug-related side effects experienced by subjects in clinical trials; or • failure of our third-party contractors and collaborators to meet their contractual obligations to us or otherwise meet their development or other objectives in a timely manner.
Moreover, President Biden signed into law the Inflation Reduction Act (IRA) on August 16, 2022, which allows Medicare to: beginning in 2026, establish a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with CMS; and, beginning in 2023, penalize drug companies that raise prices for products covered under Medicare Parts B and D faster than inflation, among other reforms.
Moreover, President Biden signed into law the Inflation Reduction Act (IRA) on August 16, 2022, which allows Medicare to: beginning in 2026, establish a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with CMS; and, beginning in 2023, penalize drug companies that raise prices for products covered under Medicare Parts B and D faster than inflation, among 35 other reforms.
If our licensors or any future licensees having rights to file, prosecute, maintain, and defend our patent rights fail to conduct these activities for patents or patent applications covering any of our drug candidates, including due to the impact of geopolitical conflict on our licensors’ business operations, our ability to develop and commercialize those drug candidates may be adversely affected and we may not be able to prevent competitors from making, using, or selling competing products.
If our licensors or any future licensees having rights to file, prosecute, maintain, and defend our patent rights fail to conduct these activities for patents or patent applications covering any of our drug candidates, including due to the impact of geopolitical conflict on our 46 licensors’ business operations, our ability to develop and commercialize those drug candidates may be adversely affected and we may not be able to prevent competitors from making, using, or selling competing products.
Although we are not currently aware of any litigation or other proceedings or third-party claims of intellectual property infringement related to our drug candidates, the pharmaceutical industry is characterized by extensive litigation regarding patents and other intellectual property rights , as well as administrative proceedings for challenging patents, including interference, derivation, inter partes review, post-grant review, and reexamination proceedings before the USPTO, or oppositions and other comparable proceedings in foreign jurisdictions, as well as administrative proceedings for challenging patents, including interference, derivation, inter partes review, post-grant review, and reexamination proceedings before the USPTO, or oppositions and other comparable proceedings in foreign jurisdictions .
Although we are not currently aware of any litigation or other proceedings or third-party claims of intellectual property infringement related to our drug candidates, the pharmaceutical industry is characterized by extensive litigation regarding patents and other intellectual property rights , as well as administrative proceedings for challenging patents, including interference, derivation, inter partes review, post-grant review, and reexamination proceedings before the USPTO, or oppositions and other comparable proceedings in foreign jurisdictions, as well as administrative proceedings for challenging patents, including interference, derivation, inter partes review, post-grant review, and reexamination proceedings before the 47 USPTO, or oppositions and other comparable proceedings in foreign jurisdictions .
Any breakdown, malicious intrusion, or computer virus could result in the impairment of key business processes or breach of data security, which could result in a material disruption of our development programs and cause interruptions in our business operations, whether due to a loss of our trade secrets or other intellectual property or lead to unauthorized disclosure of personal data of our employees, third parties with which we do business, clinical trial participants, or others.
Any breakdown, malicious 24 intrusion, or computer virus could result in the impairment of key business processes or breach of data security, which could result in a material disruption of our development programs and cause interruptions in our business operations, whether due to a loss of our trade secrets or other intellectual property or lead to unauthorized disclosure of personal data of our employees, third parties with which we do business, clinical trial participants, or others.
Since patent applications in the United States and most other countries are confidential for a period of time after filing or until issuance, we cannot be certain that we or our licensors were the first to either (i) file any patent application related to our drug candidates and other proprietary technologies we may develop or (ii) invent any of the inventions claimed in our or our licensor’s patents or patent applications.
Since patent applications in the United States and most other countries are confidential for a period of time after filing or until issuance, we cannot be certain that we or our licensors were the first to either (i) file any patent application related to our drug candidates and 43 other proprietary technologies we may develop or (ii) invent any of the inventions claimed in our or our licensor’s patents or patent applications.
On July 8, 2021, the Company, together with its wholly owned subsidiary, Prothena Biosciences Limited (“PBL”), entered into a Share Purchase Agreement with Novo Nordisk and NNRE (together with Novo Nordisk, “Buyer”), pursuant to which PBL sold and transferred to NNRE, all issued and outstanding ordinary shares of Neotope Neuroscience Limited, a wholly owned subsidiary of PBL, for an aggregate purchase price of up to $1.23 billion.
On July 8, 2021, the Company, together with its wholly owned subsidiary, Prothena Biosciences Limited (“PBL”), entered into a Share Purchase Agreement with Novo Nordisk and NNRE (together with Novo Nordisk, “Buyer”), pursuant to 41 which PBL sold and transferred to NNRE, all issued and outstanding ordinary shares of Neotope Neuroscience Limited, a wholly owned subsidiary of PBL, for an aggregate purchase price of up to $1.23 billion.
The Companies Act requires that every five years our shareholders renew the separate authorities of our Board to (a) allot and issue shares, and (b) opt out of the statutory pre-emption right that otherwise applies to share issuances for cash (which pre-emption right would require that shares issued for cash be offered to our existing shareholders on a pro rata basis before the shares may be issued to new shareholders).
The Companies Act requires that every five years our shareholders renew the separate authorities of our Board to (a) allot and issue shares, and (b) opt out of the statutory pre-emption right that otherwise applies to share issuances for cash (which pre-emption right would require that shares issued 54 for cash be offered to our existing shareholders on a pro rata basis before the shares may be issued to new shareholders).
The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology or increase what we believe to be our financial or other obligations under the relevant 50 agreement, either of which could have a material adverse effect on our business, financial condition, results of operations, and/or growth prospects.
The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology or increase what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations, and/or growth prospects.
For example, in the European Union (“EU”), the EU General Data Protection Regulation (the “EU GDPR”) governs the collection of, and other processing activities involving, personal data (i.e., data which identifies an individual or from which an individual is identifiable), including clinical trial data, and grants individuals various data protection rights (e.g., the right to the erasure of personal data).
For example, in the European Union (“EU”), the EU General Data Protection Regulation (the “EU GDPR”) governs the collection of, and other processing activities involving, personal data (i.e., data which identifies an individual or 25 from which an individual is identifiable), including clinical trial data, and grants individuals various data protection rights (e.g., the right to the erasure of personal data).
Inventorship disputes may arise from conflicting views regarding the 49 contributions of different individuals named as inventors, the effects of foreign laws where foreign nationals are involved in the development of the subject matter of the patent, conflicting obligations of third parties involved in developing our drug candidates or as a result of questions regarding co-ownership of potential joint inventions.
Inventorship disputes may arise from conflicting views regarding the contributions of different individuals named as inventors, the effects of foreign laws where foreign nationals are involved in the development of the subject matter of the patent, conflicting obligations of third parties involved in developing our drug candidates or as a result of questions regarding co-ownership of potential joint inventions.
Our research and development programs are prone to the significant and likely risks of failure inherent in drug development, which can result from the failure of the drug candidate to be sufficiently effective, the safety profile of the drug candidate, a clinical trial that is not sufficiently enrolled or powered or adequately designed to detect a drug effect, or other reasons.
Our research and development programs are prone to the significant and 26 likely risks of failure inherent in drug development, which can result from the failure of the drug candidate to be sufficiently effective, the safety profile of the drug candidate, a clinical trial that is not sufficiently enrolled or powered or adequately designed to detect a drug effect, or other reasons.
Certain of these third parties have failed to perform these activities for us and any of these third parties may fail to perform these activities for us in the future, which could cause nonclinical or clinical development of our drug candidates to be delayed, which could have an adverse effect on our business, financial condition, results of operations, and/or growth prospects.
Certain of these third parties have failed to perform these activities for us and any of these third parties may fail to perform these activities for us in the future, which could cause nonclinical or clinical development of our drug 40 candidates to be delayed, which could have an adverse effect on our business, financial condition, results of operations, and/or growth prospects.
However, the Leahy-Smith 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 48 patents, all of which could have a material adverse effect on our business, financial condition, results of operations, and/or growth prospects. Recent U.S.
However, the Leahy-Smith 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, all of which could have a material adverse effect on our business, financial condition, results of operations, and/or growth prospects. Recent U.S.
Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors. Although we have and will enter into agreements with these third parties, we will be responsible for confirming that our clinical trials are conducted in accordance with their general investigational plans and protocols.
Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors. Although we have and will enter into agreements with these third parties, we will be responsible for confirming that our clinical 39 trials are conducted in accordance with their general investigational plans and protocols.
Shareholders entitled to an exemption from Irish dividend withholding tax on any dividends received from us will not be subject to Irish income tax in respect of those dividends, unless they have some connection with Ireland other than their 60 shareholding (for example, they are resident in Ireland).
Shareholders entitled to an exemption from Irish dividend withholding tax on any dividends received from us will not be subject to Irish income tax in respect of those dividends, unless they have some connection with Ireland other than their shareholding (for example, they are resident in Ireland).
Other parties may hold or obtain patents in the future and allege that the use of our technologies infringes these patent claims or that we are employing their proprietary technology without authorization. Furthermore, patent reform and changes to patent laws add uncertainty to the possibility of 52 challenge to our patents in the future.
Other parties may hold or obtain patents in the future and allege that the use of our technologies infringes these patent claims or that we are employing their proprietary technology without authorization. Furthermore, patent reform and changes to patent laws add uncertainty to the possibility of challenge to our patents in the future.
A number of exemptions from Irish dividend withholding tax exist such that shareholders resident in the U.S. and shareholders resident in other countries that have entered into a double taxation treaty with Ireland may be entitled to exemptions from Irish dividend withholding tax subject to the completion of certain dividend withholding tax declaration forms.
A number of exemptions from Irish dividend withholding tax exist such that shareholders resident in the U.S. and shareholders resident in other countries that have entered into a double taxation treaty 55 with Ireland may be entitled to exemptions from Irish dividend withholding tax subject to the completion of certain dividend withholding tax declaration forms.
In addition, such foreign trials would be subject to the applicable local laws of 33 the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any other comparable foreign regulatory authority will accept data from trials conducted outside of its applicable jurisdiction.
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 other comparable foreign regulatory authority will accept data from trials conducted outside of its applicable jurisdiction.
Because we believe that our laboratory and materials handling policies and practices sufficiently mitigate the likelihood of materials liability or third-party claims, we currently carry no insurance covering such claims. An accident could damage, or force us to shut down, our operations.
Because we believe that our laboratory and materials handling 32 policies and practices sufficiently mitigate the likelihood of materials liability or third-party claims, we currently carry no insurance covering such claims. An accident could damage, or force us to shut down, our operations.
However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, 41 or that the FDA will not consider our drug candidates to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated.
However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider our drug candidates to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated.
Pursuant to the terms of the license agreements with some of 51 our licensors, the licensors may have the right to control enforcement of our licensed patents or defense of any claims asserting the invalidity of these patents and, even if we are permitted to pursue such enforcement or defense, we cannot ensure the cooperation of our licensors.
Pursuant to the terms of the license agreements with some of our licensors, the licensors may have the right to control enforcement of our licensed patents or defense of any claims asserting the invalidity of these patents and, even if we are permitted to pursue such enforcement or defense, we cannot ensure the cooperation of our licensors.
Although the CCPA currently exempts certain health-related information, including clinical trial data, the CCPA and the amendments under the CPRA may increase our compliance costs and potential liability. Multiple states have followed California to legislate comprehensive privacy laws with data privacy rights.
Although the CCPA exempts certain health-related information, including clinical trial data, the CCPA and the amendments under the CPRA may increase our compliance costs and potential liability. Multiple states have followed California to legislate comprehensive privacy laws with data privacy rights.
This lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval to market our drug candidates, which would significantly harm our business, results of operations, and/or growth prospects.
This lengthy, complex approval process, as well as the unpredictability of future clinical trial results, may result in our failing to obtain regulatory approval to market our drug candidates, which would significantly harm our business, results of operations, and/or growth prospects.
If we do not have sufficient patent life to protect our products, our business and results of operations will be adversely affected. We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.
If we do not have sufficient patent life to protect our products, our business and results of operations will be adversely affected. 44 We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.
Composition-of-matter patents on the biological or chemical active pharmaceutical ingredient are generally considered to be the strongest form of intellectual property protection for pharmaceutical products, as such patents provide protection without regard to any method of use.
Composition-of-matter patents on the biological or chemical active pharmaceutical 42 ingredient are generally considered to be the strongest form of intellectual property protection for pharmaceutical products, as such patents provide protection without regard to any method of use.
Marketing applications filed by sponsors of products granted Fast Track designation may qualify for priority review under FDA policies and procedures, but Fast Track designation does not assure any such review or ultimate marketing approval by the FDA.
Marketing 37 applications filed by sponsors of products granted Fast Track designation may qualify for priority review under FDA policies and procedures, but Fast Track designation does not assure any such review or ultimate marketing approval by the FDA.
Method-of-use patents protect the use of a product 47 for the specified method. This type of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method.
Method-of-use patents protect the use of a product for the specified method. This type of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method.
These requirements include submissions of safety and other post- 34 marketing information and reports, as well as continued compliance with current good manufacturing practice (“cGMP”) requirements and current good clinical practice (“cGCP”) requirements for any clinical trials that we conduct.
These requirements include submissions of safety and other post-marketing information and reports, as well as continued compliance with current good manufacturing practice (“cGMP”) requirements and current good clinical practice (“cGCP”) requirements for any clinical trials that we conduct.
Our collaboration with Roche is complex, particularly with respect to future U.S. commercialization of prasinezumab, with respect to financial provisions, allocations of responsibilities, cost estimates, and 36 the respective rights of the parties in decision making.
Our collaboration with Roche is complex, particularly with respect to future U.S. commercialization of prasinezumab, with respect to financial provisions, allocations of responsibilities, cost estimates, and the respective rights of the parties in decision making.
If we are unable to prevent unauthorized material disclosure of our intellectual property to third parties, or misappropriation of our intellectual property by third parties, we will not be able to establish or maintain a competitive advantage in our market, which could materially adversely affect our business, operating results, and financial condition. 54 We may be subject to claims that our employees, collaborators, partners, contractors, or advisors have wrongfully used or disclosed alleged trade secrets of third parties.
If we are unable to prevent unauthorized material disclosure of our intellectual property to third parties, or misappropriation of our intellectual property by third parties, we will not be able to establish or maintain a competitive advantage in our market, which could materially adversely affect our business, operating results, and financial condition. 49 We may be subject to claims that our employees, collaborators, partners, contractors, or advisors have wrongfully used or disclosed alleged trade secrets of third parties.
Our future capital requirements will depend on many factors that are currently unknown to us, including, without limitation: • the timing of progress, results, and costs of our clinical trials, including the Phase 3 clinical trial for birtamimab, the Phase 2 clinical trial for prasinezumab being conducted by Roche, the Phase 2b clinical trial for prasinezumab being conducted by Roche, the Phase 2 clinical trial f or coramitug (formerly PRX004) bei ng conducted by Novo Nordisk, the Phase 2 clinical trial for BMS-986446 being conducted by BMS, the Phase 1 clinical trials for PRX012, and the Phase 1 clinical trial for PRX019; • the timing, initiation, progress, results, and costs of these and our other research, development, and possible commercialization activities; • the results of our research, nonclinical studies, and clinical trials; 24 • the costs of manufacturing our drug candidates for clinical development as well as for future commercialization needs; • if and when appropriate, the costs of preparing for commercialization of our drug candidates; • the costs of preparing, filing, and prosecuting patent applications, and maintaining, enforcing, and defending intellectual property-related claims; • our ability to establish strategic collaborations, licensing, or other arrangements; • the timing, receipt, and amount of any capital investments, cost-sharing contributions or reimbursements, milestone payments, or royalties that we might receive under current or potential future collaborations; • the costs to satisfy our obligations under current and potential future collaborations; and • the timing, receipt, and amount of revenues or royalties, if any, from any approved drug candidates.
Our future capital requirements will depend on many factors that are currently unknown to us, including, without limitation: • the timing of progress, results, and costs of our clinical trials, including the Phase 3 clinical trial for prasinezumab being conducted by Roche, the Phase 3 clinical trial f or coramitug (formerly PRX004) bei ng conducted by Novo Nordisk, the Phase 2 clinical trial for BMS-986446 being conducted by BMS, and the Phase 1 clinical trial for PRX019; • the timing, initiation, progress, results, and costs of these and our other research, development, and possible commercialization activities; • the results of our research, nonclinical studies, and clinical trials; • the costs of manufacturing our drug candidates for clinical development as well as for future commercialization needs; • if and when appropriate, the costs of preparing for commercialization of our drug candidates; • the costs of preparing, filing, and prosecuting patent applications, and maintaining, enforcing, and defending intellectual property-related claims; • our ability to establish strategic collaborations, licensing, or other arrangements; • the timing, receipt, and amount of any capital investments, cost-sharing contributions or reimbursements, milestone payments, or royalties that we might receive under current or potential future collaborations; • the costs to satisfy our obligations under current and potential future collaborations; and • the timing, receipt, and amount of revenues or royalties, if any, from any approved drug candidates.
Adequate third-party reimbursement might not be available to enable us to maintain price levels 38 sufficient to realize an appropriate return on investment in product development.
Adequate third-party reimbursement might not be available to enable us to maintain price levels sufficient to realize an appropriate return on investment in product development.
For example, Washington 27 recently passed the My Health My Data Act, which has a broader scope than HIPAA and includes a private right of action.
For example, Washington recently passed the My Health My Data Act, which has a broader scope than HIPAA and includes a private right of action.
In the U.S., this must be done to the satisfaction of the FDA; in the EU, this must be 29 done to the satisfaction of the European Medicines Agency (the “EMA”); and in other countries this must be done to the satisfaction of comparable regulatory authorities.
In the U.S., this must be done to the satisfaction of the FDA; in the EU, this must be done to the satisfaction of the European Medicines Agency (the “EMA”); and in other countries this must be done to the satisfaction of comparable regulatory authorities.
We do not believe we were a PFIC for U.S. federal income tax purposes for our taxable year ended December 31, 2024. However, the application of the PFIC rules is subject to uncertainties in a number of respects, and we cannot assure that the U.S. Internal Revenue Service (the “IRS”) will not take a contrary position.
We do not believe we were a PFIC for U.S. federal income tax purposes for our taxable year ended December 31, 2025. However, the application of the PFIC rules is subject to uncertainties in a number of respects, and we cannot assure that the U.S. Internal Revenue Service (the “IRS”) will not take a contrary position.
We have been, and may in the future be, adversely affected by business disruptions beyond our control, including outbreaks of epidemic, pandemic, or contagious disease, geopolitical turmoil, earthquakes or other natural disasters, and adverse weather events, including as a result of climate change.
We have been, and may in the future be, adversely affected by business disruptions beyond our control, including outbreaks of epidemic, pandemic, or contagious disease, trade policies or geopolitical turmoil, earthquakes or other natural disasters, and adverse weather events, including as a result of climate change.
Pillar Two has been implemented into Irish law with effect for periods 58 beginning on or after December 31, 2023.
Pillar Two has been implemented into Irish law with effect for periods beginning on or after December 31, 2023.
A material weakness in internal control over financial reporting is a deficiency, 57 or a combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of a company’s annual or interim consolidated financial statements will not be prevented or detected on a timely basis by the company’s internal controls.
A material weakness in internal control over financial reporting is a deficiency, 52 or a combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of a company’s annual or interim consolidated financial statements will not be prevented or detected on a timely basis by the company’s internal controls.
We cannot predict whether we, or our partners (as applicable), will encounter problems with the Phase 3 clinical trial for birtamimab, the Phase 2 clinical trial for prasinezumab, the Phase 2b clinical trial for prasinezumab, the Phase 2 clinical trial f or coramitug , t he Phase 2 clinical trial for BMS-986446, the Phase 1 clinical trials for PRX012, the Phase 1 clinical trial for PRX019, or any other future clinical trials that will cause us or any regulatory authority to delay, suspend or terminate those clinical trials or delay the analysis of data derived from them.
We cannot predict whether we, or our partners (as applicable), will encounter problems with the Phase 3 clinical trial for prasinezumab, the Phase 3 clinical trial f or coramitug , t he Phase 2 clinical trial for BMS-986446, the Phase 1 clinical trial for PRX019, or any other future clinical trials that will cause us or any regulatory authority to delay, suspend or terminate those clinical trials or delay the analysis of data derived from them.
Kinney or any other person on whom we are highly dependent might impede the achievement of our research, development, and commercial objectives. We do not carry “key person” insurance covering any members of our senior management. Attracting and retaining qualified scientific and other personnel are critical to our growth and future success.
The loss of the services of Dr. Kinney or any other person on whom we are highly dependent might impede the achievement of our research, development, and commercial objectives. We do not carry “key person” insurance covering any members of our senior management. Attracting and retaining qualified scientific and other personnel are critical to our growth and future success.
We are dependent upon Novo Nordisk with respect to further developme nt of coramitug , includin g the Phase 2 clinical trial and any future clinical trial of that drug candidate.
We are dependent upon Novo Nordisk with respect to further developme nt of coramitug , includin g the Phase 3 clinical trial and any future clinical trial of that drug candidate.
Any one or more of these force majeure events could have a material adverse effect on our liquidity, results of operations, financial condition or business, including the progress of, and timelines for, our nonclinical and clinical development programs, and may create safety challenges for our employees and safe occupancy of our job sites, financial market volatility and significant macroeconomic uncertainty in global markets.
Any one or more of these force majeure events could have a material adverse effect on our liquidity, results of operations, financial condition or business, including the progress of, and timelines for, our nonclinical and clinical development programs, and may create safety challenges for our employees and safe occupancy of our job sites, financial market volatility, barriers to international trade, and significant macroeconomic uncertainty in global markets.
Our drug candidates could fail to receive regulatory approval for many reasons, including the following: • the FDA, the EMA, or comparable regulatory authorities may disagree with the design, implementation, or conduct of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA, the EMA, or comparable regulatory authorities that a drug candidate is safe and effective for its proposed indication; • the results of clinical trials may not meet the level of statistical significance required by the FDA, the EMA, or comparable regulatory authorities for approval; • we may be unable to demonstrate that a drug candidate’s clinical and other benefits outweigh its safety risks; • the FDA, the EMA, or comparable regulatory authorities may disagree with our interpretation of data from nonclinical studies or clinical trials; • the data collected from clinical trials of our drug candidates may not be sufficient to support the submission of an NDA or a BLA to the FDA, a Marketing Authorization Application (“MAA”) to the EMA, or similar applications to comparable regulatory authorities; • the FDA, the EMA, or comparable regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; or • the approval policies or regulations of the FDA, the EMA, or comparable regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Our drug candidates could fail to receive regulatory approval for many reasons, including the following: • the FDA, the EMA, or comparable regulatory authorities may disagree with the design, implementation, or conduct of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA, the EMA, or comparable regulatory authorities that a drug candidate is safe and effective for its proposed indication; • the results of clinical trials may not meet the level of statistical significance required by the FDA, the EMA, or comparable regulatory authorities for approval; • we may be unable to demonstrate that a drug candidate’s clinical and other benefits outweigh its safety risks; • the FDA, the EMA, or comparable regulatory authorities may disagree with our interpretation of data from nonclinical studies or clinical trials; • the data collected from clinical trials of our drug candidates may not be sufficient to support the submission of a Biologics License Application (“BLA”) or a New Drug Application (“NDA”) to the FDA, a Marketing Authorization Application (“MAA”) to the EMA, or similar applications to comparable regulatory authorities; • the FDA, the EMA, or comparable regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; or • the approval policies or regulations of the FDA, the EMA, or comparable regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
There can be no assurance that such remaining milestones 46 will be met.
There can be no assurance that such remaining milestones will be met.
There can be no assurance that our drug candidates, if they are approved for sale in the U.S. or in other countries, will be considered medically reasonable and necessary for a specific indication, that they will be considered cost-effective by third-party payers, that coverage or an adequate level of reimbursement will be available, or that third-party payers’ reimbursement policies will not adversely affect our ability to sell our drug candidates profitably if they are approved for sale. 40 The markets for our drug candidates are subject to intense competition.
There can be no assurance that our drug candidates, if they are approved for sale in the U.S. or in other countries, will be considered medically reasonable and necessary for a specific indication, that they will be considered cost-effective by third-party payers, that coverage or an adequate level of reimbursement will be available, or that third-party payers’ reimbursement policies will not adversely affect our ability to sell our drug candidates profitably if they are approved for sale.
In addition, even if we were to obtain approval, regulatory authorities may approve any of our drug candidates for fewer or more limited indications than we request, may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve a drug candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that drug candidate.
In addition, even if we were to obtain approval, regulatory authorities may approve any of our drug candidates for fewer or more limited indications than we request, may grant approval contingent on the performance of costly post-approval clinical 30 trials or other post-approval commitments or requirements, or may approve our drug candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that drug candidate.
A transfer of our ordinary shares (i) by a seller who holds shares outside of DTC to any buyer, or (ii) by a seller who holds the shares through DTC to a buyer who holds the acquired shares outside of DTC, may be subject to Irish stamp duty.
A transfer of our ordinary shares (i) by a seller who holds shares outside of DTC to any buyer, or (ii) by a seller who holds the shares through DTC to a buyer who holds the acquired shares outside of DTC, may be subject to Irish stamp duty, subject to the availability of a relief or exemption.
We may not generate the cash that is necessary to finance our operations in the foreseeable future. We incurred net lo sses of $122.3 million, $147.0 million and $116.9 million for the years ended December 31, 2024 , 2023, and 2022 , respectively. As of December 31, 2024 , we had an accumulated deficit of $1.1 billion .
We may not generate the cash that is necessary to finance our operations in the foreseeable future. We incurred net lo sses of $244.1 million $122.3 million and $147.0 million for the years ended December 31, 2025, 2024, and 2023, respectively. As of December 31, 2025, we had an accumulated deficit of $1.3 billion.
There is no assurance that the results of the Phase 3 clinical trial for birtamimab, the Phase 2 clinical trial for prasinezumab, the Phase 2b clinical trial for prasinezumab, the Phase 2 clinical tr ial for coramitug , the Ph ase 2 clinical trial for BMS-986446, the Phase 1 clinical trials for PRX012, and the Phase 1 clinical trial for PRX019 will support further development of these drug candidates.
There is no assurance that the results of the Phase 3 clinical trial for prasinezumab, the Phase 3 clinical tr ial for coramitug , the Ph ase 2 clinical trial for BMS-986446, and the Phase 1 clinical trial for PRX019 will support further development of these drug candidates.
For example, the Phase 3 clinical trial for birtamimab has clinical trial sites located globally, including in Israel and Eastern Europe, and operations at such clinical trial sites may be disrupted by ongoing conflicts and/or new conflicts, which could result in (i) the inability or unwillingness of study participants, site investigators or other study personnel to travel to such clinical trial sites or otherwise follow study protocols, (ii) the diversion of healthcare resources away from the conduct of clinical trials, or (iii) the complete or partial cessation of operations at such clinical trial sites. 26 • Our key research facility and a significant portion of our operations are in the San Francisco Bay Area of Northern California, which in the past has experienced severe earthquakes.
For example, operations at clinical trial sites may be disrupted by ongoing conflicts and/or new conflicts, which could result in (i) the inability or unwillingness of study participants, site investigators or other study personnel to travel to such clinical trial sites or otherwise follow study protocols, (ii) the diversion of healthcare resources away from the conduct of clinical trials, or (iii) the complete or partial cessation of operations at such clinical trial sites. • Our key research facility and a significant portion of our operations are in the San Francisco Bay Area of Northern California, which in the past has experienced severe earthquakes.
Our patents issued as of December 31, 2024, are anticipated to expire on dates ranging from 2025 to 2042, subject to any patent extensions that may be available for such patents. If patents are issued on our patent applications pending as of December 31, 2024, the resulting patents are projected to expire on dates ranging from 2025 to 2045.
Our patents issued as of December 31, 2025, are anticipated to expire on dates ranging from 2026 to 2042, subject to any patent extensions that may be available for such patents. If patents are issued on our patent applications pending as of December 31, 2025, the resulting patents are projected to expire on dates ranging from 2028 to 2046.
We expect to continue to incur substantial losses for the foreseeable future as we: • support the Phase 3 AFFIRM-AL clinical trial for birtamimab, the Phase 1 clinical trials for PRX012, the Phase 1 clinical trial for PRX019, and potential additional clinical trials for these and other programs, including PRX123; • develop and possibly commercialize our drug candidates, including birtamimab, PRX012, and PRX123; • undertake nonclinical development of other drug candidates and initiate clinical trials, if supported by nonclinical data; • pursue our early stage research and seek to identify additional drug candidates; and • potentially acquire rights from third parties to drug candidates or technologies through licenses, acquisitions, or other means.
We expect to continue to incur substantial losses for the foreseeable future as we: • wind down the Phase 1 clinical trials for PRX012, and support the Phase 1 clinical trial for PRX019 and potential additional clinical trials for these and other programs; • develop and possibly commercialize our drug candidates; • undertake nonclinical development of other drug candidates and initiate clinical trials, if supported by nonclinical data; • pursue our early stage research and seek to identify additional drug candidates; and 21 • potentially acquire rights from third parties to drug candidates or technologies through licenses, acquisitions, or other means.
In addition, if we do not obtain a license, develop or obtain non-infringing technology, fail to defend an infringement action successfully, or have infringed patents declared invalid, we may: • incur substantial monetary damages, including treble damages and attorneys’ fees for willful infringement; • obtain one or more licenses from third parties and potentially pay royalties; • redesign our infringing products, which may be impossible on a cost-effective basis or require substantial time and monetary expenditure; • encounter significant delays in bringing our drug candidates to market; and/or • be precluded from participating in the manufacture, use, or sale of our drug candidates or methods of treatment requiring licenses. 53 In that event, we would be unable to further develop and commercialize our drug candidates, which could harm our business significantly.
In addition, if we do not obtain a license, develop or obtain non-infringing technology, fail to defend an infringement action successfully, or have infringed patents declared invalid, we may: • incur substantial monetary damages, including treble damages and attorneys’ fees for willful infringement; • obtain one or more licenses from third parties and potentially pay royalties; • redesign our infringing products, which may be impossible on a cost-effective basis or require substantial time and monetary expenditure; • encounter significant delays in bringing our drug candidates to market; and/or 48 • be precluded from participating in the manufacture, use, or sale of our drug candidates or methods of treatment requiring licenses.
We are dependent upon Roche with respect to further development of prasinezumab. Under the terms of our collaboration with Roche, Roche is responsible for that further development, including the conduct of the ongoing Phase 2 and Phase 2b clinical trials and any future clinical trial of that drug candidate.
We are dependent upon Roche with respect to further development of prasinezumab. Under the terms of our collaboration with Roche, Roche is responsible for that further development, including the conduct of the Phase 3 clinical trial and any future clinical trial of that drug candidate.
We are dependent on Novo Nordisk, and its third-party manufacturers if applicable, to manufacture clinical supplies of coramitug . We are dependent on BMS, and its third-party manufacturers if applicable, to manufacture clinical supplies of BMS-986446.
We are dependent on BMS, and its third-party manufacturers if applicable, to manufacture clinical supplies of BMS-986446.
We will require additional capital to fund our operations, and if we are unable to obtain such capital, we will be unable to successfully develop and commercialize drug candidates. As of December 31, 2024, we had cash and cash equivalents o f $471.4 million .
We will require additional capital to fund our operations, and if we are unable to obtain such capital, we will be unable to successfully develop and commercialize drug candidates. As of December 31, 2025, we had cash and cash equivalents o f $307.5 million.
As a result of the COVID-19 pandemic, we may also face increased cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
We may also face increased cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
As of December 31, 2024, the number of ordinary shares available for issuance pursuant to outstanding and future equity awards under our equity plans was 15,332,174 . If we are unable to maintain effective internal controls, our business could be adversely affected. We are subject to the reporting and other obligations under the U.S.
As of December 31, 2025, the number of ordinary shares available for issuance pursuant to outstanding and future equity awards under our equity plans was 16,780,773. If we are unable to maintain effective internal controls, our business could be adversely affected. We are subject to the reporting and other obligations under the U.S.
Payment of any Irish stamp duty is generally a legal obligation of the transferee. Any Irish stamp duty payable on transfers of our ordinary shares could adversely affect the price of those shares. We do not anticipate paying cash dividends, and accordingly, shareholders must rely on ordinary share appreciation for any return on their investment.
Any Irish stamp duty payable on transfers of our ordinary shares could adversely affect the price of those shares. We do not anticipate paying cash dividends, and accordingly, shareholders must rely on ordinary share appreciation for any return on their investment.
A Fast Track designation by the FDA, even if granted for current or future drug candidates, may not lead to a faster development or regulatory review, licensure process and does not increase the likelihood that our drug candidates will receive marketing licensure.
A Fast Track designation by the FDA, even if granted for current or future drug candidates, may not lead to a faster development or regulatory review, licensure process and does not increase the likelihood that our drug candidates will receive marketing licensure. BMS-986446, for the treatment of Alzheimer’s disease, has been granted Fast Track Designation by the FDA.
Additionally, the Colorado Privacy Act and Connecticut Personal Data Privacy and Online Monitoring Act went into effect on July 1, 2023. While these new laws generally include exemptions for HIPAA-covered and clinical trial data, they impact the overall privacy landscape. Several other states have followed suit and passed similar legislation which will go into effect in the coming years.
For example, the Virginia Consumer Data Protection Act, the Colorado Privacy Act, and Connecticut Personal Data Privacy and Online Monitoring Act. While these new laws generally include exemptions for HIPAA-covered and clinical trial data, they impact the overall privacy landscape. Several other states have followed suit and passed similar legislation which will go into effect in the coming years.
The CCPA, among other things, imposes new data privacy obligations on covered companies and provides expanded privacy rights to California residents, including the right to access, delete, and opt out of certain disclosures of their information.
For example, the California Consumer Privacy Act (the “CCPA”), among other things, imposes data privacy obligations on covered companies and provides expanded privacy rights to California residents, including the right to access, delete, and opt out of certain disclosures of their information.
We are dependent on Catalent Pharma and Sharp Sterile to manufacture these clinical supplies. Lonza Ltd (“Lonza”) is our third-party manufacturer of clinical supplies of our drug candidate PRX019. We are dependent on Lonza to manufacture these clinical supplies. We are dependent on Roche, and its third-party manufacturers if applicable, to manufacture clinical supplies of prasinezumab.
Lonza Ltd (“Lonza”) is our third-party manufacturer of clinical supplies of our drug candidate PRX019. We are dependent on Lonza to manufacture these clinical supplies. We are dependent on Roche, and its third-party manufacturers if applicable, to manufacture clinical supplies of prasinezumab. We are dependent on Novo Nordisk, and its third-party manufacturers if applicable, to manufacture clinical supplies of coramitug.
If we fail to comply with these obligations , including due to our use of the intellectual property licensed to us in an unauthorized manner, and fail to cure our breach within a specified period of time, the licensor may have the right to terminate the applicable license, in which event we could lose valuable rights and technology that are material to our business , harming our ability to develop, manufacture, and/or commercialize our platform or drug candidates .
If we fail to comply with these obligations , including due to our use of the intellectual property licensed to us in an unauthorized manner, and fail to cure our breach within a specified period of time, the licensor may have the right to terminate the applicable license, in which event we could lose valuable rights and technology that are material to our business , harming our ability to develop, manufacture, and/or commercialize our platform or drug candidates . 45 In addition, the agreements under which we license intellectual property or technology to or from third parties are complex, and certain provisions in such agreements may be susceptible to multiple interpretations.
In order to market any products that may be approved by the FDA, the EMA, or other comparable regulatory authorities, we must build our sales, marketing, managerial, and other non-technical capabilities or make arrangements with third parties to perform these services.
We do not currently have a fully-scaled organization for the sales, marketing, and distribution of pharmaceutical products. In order to market any products that may be approved by the FDA, the EMA, or other comparable regulatory authorities, we must build our sales, marketing, managerial, and other non-technical capabilities or make arrangements with third parties to perform these services.
As a result of Pillar Two or other policy changes, whether at national or supranational level, the tax laws in Ireland, the U.S., and other countries in which we do business could change on a prospective or retroactive basis, and any such changes could have an adverse effect on our business, financial condition, results of operations, and/or growth prospects.
As a result of Pillar Two or other policy changes, whether at national or supranational level, the tax laws in Ireland, the U.S., and other countries in which we do business could change on a prospective or retroactive basis, and any such changes could have an adverse effect on our business, financial condition, results of operations, and/or growth prospects. 53 Irish law differs from the laws in effect in the United States and may afford less protection to holders of our ordinary shares.
We are highly dependent on key personnel, including Dr. Gene G. Kinney, our President and Chief Executive Officer. There can be no assurance that we will be able to retain Dr. Kinney or any of our key personnel. The loss of the services of Dr.
Our future success depends on our ability to retain key personnel and to attract, retain, and motivate qualified personnel. We are highly dependent on key personnel, including Dr. Gene G. Kinney, our President and Chief Executive Officer. There can be no assurance that we will be able to retain Dr. Kinney or any of our key personnel.

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Item 2. Properties

Properties — owned and leased real estate

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Biggest changeITEM 2. PROPERTIES Our corporate registered address and office is in Dublin, Ireland and our U.S. operations are in Brisbane, California. In Dublin, Ireland, we occupy approximately 920 square feet of office spaces under two leases which expire on July 31, 2025.
Biggest changeITEM 2. PROPERTIES Our corporate registered address and office is in Dublin, Ireland and our U.S. operations are in Brisbane, California. 56 In Dublin, Ireland, we occupy approximately 920 square feet of office spaces under two leases which expire on July 31, 2026.
In Brisbane, California, we occupy approximately 31,157 square feet of office and laboratory space under a sublease with Arcus Biosciences, Inc. which expires on September 30, 2028, unless terminated earlier. 61 We believe that our facilities are sufficient to meet our current needs.
In Brisbane, California, we occupy approximately 31,157 square feet of office and laboratory space under a sublease with Arcus Biosciences, Inc. which expires on September 30, 2028, unless terminated earlier. We believe that our facilities are sufficient to meet our current needs.

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. We may at times be party to ordinary routine litigation incidental to our business. When appropriate in management’s estimation, we may record reserves in our financial statements for pending legal proceedings. ITEM 4. MINE SAFETY DISCLOSURES Not Applicable. 62 PART II
Biggest changeITEM 3. LEGAL PROCEEDINGS We are not currently a party to any material legal proceedings. We may at times be party to ordinary routine litigation incidental to our business. When appropriate in management’s estimation, we may record reserves in our financial statements for pending legal proceedings. ITEM 4. MINE SAFETY DISCLOSURES Not Applicable. 57 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changePoints on the graph represent the performance as of end of each business day. 63 COMPARISON OF 5-YEAR CUMULATIVE TOTAL RETURN Among Prothena Corporation plc, the Nasdaq Composite Index, and the Nasdaq Biotechnology Index Cumulative Total Return as of 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 Prothena Corporation plc $ 100 $ 76 $ 312 $ 381 $ 230 $ 87 Nasdaq Composite Index $ 100 $ 144 $ 174 $ 117 $ 167 $ 215 Nasdaq Biotechnology Index $ 100 $ 126 $ 125 $ 111 $ 115 $ 114 (1) The information under the heading “Performance Graph” shall not be deemed “soliciting material” or to be “filed” with the SEC for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities under that Section, and shall not be deemed incorporated by reference into any filing of Prothena Corporation plc under the Securities Act of 1933, as amended.
Biggest changePoints on the graph represent the performance as of end of each business day. 58 COMPARISON OF 5-YEAR CUMULATIVE TOTAL RETURN Among Prothena Corporation plc, the Nasdaq Composite Index, and the Nasdaq Biotechnology Index Cumulative Total Return as of 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 12/31/2025 Prothena Corporation plc $ 100 $ 411 $ 502 $ 303 $ 115 $ 80 Nasdaq Composite Index $ 100 $ 121 $ 81 $ 116 $ 150 $ 180 Nasdaq Biotechnology Index $ 100 $ 99 $ 89 $ 92 $ 91 $ 120 (1) The information under the heading “Performance Graph” shall not be deemed “soliciting material” or to be “filed” with the SEC for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities under that Section, and shall not be deemed incorporated by reference into any filing of Prothena Corporation plc under the Securities Act of 1933, as amended.
At present, the Transfers Act prohibits financial transfers involving the late Slobodan Milosevic and associated persons, certain persons indicted by the International Criminal Tribunal for the former Yugoslavia, the late Osama bin Laden, Al-Qaida, the Taliban of 64 Afghanistan, certain persons, entities, and activities in Burma (Myanmar), Belarus, Democratic Republic of Congo, Democratic People’s Republic of Korea (North Korea), Iran, Iraq, Côte d’Ivoire, Lebanon, Liberia, Zimbabwe, Sudan, Somalia, Republic of Guinea, Afghanistan, Egypt, Eritrea, Libya, Syria, Tunisia, Ukraine, Russia, certain known terrorists and terrorist groups, and countries that harbor certain terrorist groups, without the prior permission of the Central Bank of Ireland.
At present, the Transfers Act prohibits financial transfers involving the late Slobodan Milosevic and associated persons, certain persons indicted by the International Criminal Tribunal for the former Yugoslavia, the late Osama bin Laden, Al-Qaida, the Taliban of 59 Afghanistan, certain persons, entities, and activities in Burma (Myanmar), Belarus, Democratic Republic of Congo, Democratic People’s Republic of Korea (North Korea), Iran, Iraq, Côte d’Ivoire, Lebanon, Liberia, Zimbabwe, Sudan, Somalia, Republic of Guinea, Afghanistan, Egypt, Eritrea, Libya, Syria, Tunisia, Ukraine, Russia, certain known terrorists and terrorist groups, and countries that harbor certain terrorist groups, without the prior permission of the Central Bank of Ireland.
While the U.S./Ireland Double Tax Treaty contains provisions regarding withholding, due to the wide scope of the exemptions from DWT available under Irish domestic law, it would generally be unnecessary for a U.S. resident shareholder to rely on the treaty provisions.
While the U.S./Ireland Double Tax Treaty contains provisions regarding withholding tax on dividends, due to the wide scope of the exemptions from DWT available under Irish domestic law, it would generally be unnecessary for a U.S. resident shareholder to rely on the treaty provisions.
Our shareholders should consult their own tax advisers as to whether CAT is creditable or deductible in computing any domestic tax liabilities. 65 Stamp Duty Irish stamp duty may be payable in respect of transfers of our ordinary shares (currently at the rate of 1% of the price paid or the market value of the shares acquired, if greater).
Our shareholders should consult their own tax advisers as to whether CAT is creditable or deductible in computing any domestic tax liabilities. 60 Stamp Duty Irish stamp duty may be payable in respect of transfers of our ordinary shares (currently at the rate of 1% of the price paid or the market value of the shares acquired, if greater).
Performance Graph (1) The following graph shows a comparison from December 31, 2019, through December 31, 2024, of cumulative total return on assumed investment of $100.00 in cash in our ordinary shares, the Nasdaq Composite Index and the Nasdaq Biotechnology Index. Such returns are based on historical results and are not intended to suggest future performance.
Performance Graph (1) The following graph shows a comparison from December 31, 2020, through December 31, 2025, of cumulative total return on assumed investment of $100.00 in cash in our ordinary shares, the Nasdaq Composite Index and the Nasdaq Biotechnology Index. Such returns are based on historical results and are not intended to suggest future performance.
A transfer of our ordinary shares (i) by a seller who holds shares outside of DTC to any buyer, or (ii) by a seller who holds the shares through DTC to a buyer who holds the acquired shares outside of DTC, may be subject to Irish stamp duty.
A transfer of our ordinary shares (i) by a seller who holds shares outside of DTC to any buyer, or (ii) by a seller who holds the shares through DTC to a buyer who holds the acquired shares outside of DTC, may be subject to Irish stamp duty, subject to the availability of relief or exemption.
Holders There were approximately 5,177 shareholders of record of our ordinary shares as of February 20, 2025. Because many of our shares are held by brokers and other institutions on behalf of shareholders, we are unable to estimate the total number of shareholders represented by these record holders.
Holders There were approximately 5,106 shareholders of record of our ordinary shares as of February 20, 2026. Because many of our shares are held by brokers and other institutions on behalf of shareholders, we are unable to estimate the total number of shareholders represented by these record holders.

Item 7. Management's Discussion & Analysis

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

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Biggest changeLiquidity and Capital Resources Overview December 31, 2024 2023 (Dollars in thousands) Working capital $ 436,911 $ 582,391 Cash and cash equivalents $ 471,388 $ 618,830 Total assets $ 547,108 $ 696,382 Total liabilities $ 60,182 $ 135,017 Total shareholders’ equity $ 486,926 $ 561,365 Working capital was $436.9 million as of December 31, 2024 , a decrease of $145.5 million from working capital of $582.4 million as of December 31, 2023 .
Biggest changeManagement’s Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations” in our 2024 Annual Report on Form 10-K for a discussion of the results of operations for the year ended December 31, 2024 compared to the year ended December 31, 2023. 65 Liquidity and Capital Resources Overview December 31, 2025 2024 (Dollars in thousands) Working capital $ 274,350 $ 436,911 Cash and cash equivalents $ 307,531 $ 471,388 Total assets $ 326,804 $ 547,108 Total liabilities $ 46,330 $ 60,182 Total shareholders’ equity $ 280,474 $ 486,926 Working capital was $274.4 million as of December 31, 2025, a decrease of $162.6 million from working capital of $436.9 million as of December 31, 2024.
In general, we consider such milestone payments as variable consideration with constraint and therefore we recognize the revenue from such milestone payments as collaboration revenue at point in time when we can conclude it is probable that a significant revenue reversal will not occur in future periods. Research and Development We expense R&D costs as incurred.
In general, we consider such milestone payments as variable consideration with constraint and therefore we recognize the revenue from such milestone payments as collaboration revenue at the point in time when we can conclude it is probable that a significant revenue reversal will not occur in future periods. Research and Development We expense R&D costs as incurred.
We expect to continue to finance future capital needs that exceed our existing cash and cash equivalents, payments pursuant to our agreements with Roche, BMS, and Novo Nordisk, and, to the extent necessary, other collaboration agreements with corporate partners, or other arrangements, and through proceeds from public or private equity or debt financings, and loans, including pursuant to the Amended Distribution Agreement (See Note 8, “Shareholders’ Equity” to the Consolidated Financial Statements for more information).
We expect to continue to finance future capital needs that exceed our existing cash and cash equivalents, payments pursuant to our agreements with Roche, BMS, and Novo Nordisk, and, to the extent necessary, other collaboration agreements with corporate partners, or other arrangements, and through proceeds from public or private equity or debt financings, and loans, including pursuant to the Amended Distribution Agreement (See Note 8, “Shareholders’ Equity” to our Consolidated Financial Statements for more information).
Purchase obligations consist of non-cancelable purchase commitments to suppliers. Operating leases represent our future minimum rental commitments under our non-cancelable operating leases. For additional information regarding the timing for our contractual obligations see Note 6, “Commitments and Contingencies” to Consolidated Financial Statements.
Purchase obligations consist of non-cancelable purchase commitments to suppliers. Operating leases represent our future minimum rental commitments under our non-cancelable operating leases. For additional information regarding the timing for our contractual obligations see Note 6, “Commitments and Contingencies” to our Consolidated Financial Statements.
Our future capital requirements will depend on numerous factors, including, without limitation, the timing of initiation, progress, results and costs of our clinical trials; the results of our research and nonclinical studies; the costs of clinical manufacturing and of establishing commercial manufacturing arrangements; the costs of preparing, filing and prosecuting patent applications and maintaining, enforcing and defending intellectual property-related claims; the costs and timing of capital asset purchases; our ability to establish research collaborations, strategic collaborations, licensing or other arrangements; the costs to satisfy our obligations under current and potential future collaborations; the costs of any in-licensing transactions; and the timing, receipt, and amount of revenues or royalties, if any, from any approved drug candidates.
Our future capital requirements will depend on numerous factors, including, without limitation, the timing of initiation, progress, results and costs of our clinical trials; the results of our research and nonclinical studies; the costs of clinical manufacturing; the costs of preparing, filing and prosecuting patent applications and maintaining, enforcing and defending intellectual property-related claims; the costs and timing of capital asset purchases; our ability to establish research collaborations, strategic collaborations, licensing or other arrangements; the costs to satisfy our obligations under current and potential future collaborations; the costs of any in-licensing transactions; and the timing, receipt, and amount of revenues or royalties, if any, from any approved drug candidates.
See Note 7, “Significant Agreements” to our Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information. Pursuant to the share purchase agreement with Novo Nordisk, we are eligible to receive development and sales milestone payments. See Note 7, “Significant Agreements” to our Consolidated Financial Statements regarding the Novo Nordisk Share Purchase Agreement for more information.
See Note 7, “Significant Agreements” to our Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information. Pursuant to the share purchase agreement with Novo Nordisk, we are eligible to receive development and sales 66 milestone payments. See Note 7, “Significant Agreements” to our Consolidated Financial Statements regarding the Novo Nordisk Share Purchase Agreement for more information.
Because of the numerous risks and uncertainties associated with the development and commercialization of our product candidates, we are unable to estimate the amounts of increased capital outlays and operating expenses associated with completing the development of our product candidates.
Because of the numerous risks and uncertainties associated with the development of our product candidates, we are unable to estimate the amounts of increased capital outlays and operating expenses associated with completing the development of our product candidates.
The measurement of these research and development costs and/or effort can impact the research and development expenses in the Consolidated Statements of Operations and of prepaid assets and accrued liabilities on the 67 Consolidated Balance Sheets.
The measurement of these research and development costs and/or effort can impact the research and development expenses in the Consolidated Statements of Operations and of prepaid assets and accrued liabilities on the Consolidated Balance Sheets.
The level of judgment required to estimate research and development expenses varies based on the nature of the services being performed and the underlying support obtained.
The level of judgment required to estimate research and development expenses varies based on 62 the nature of the services being performed and the underlying support obtained.
Off-Balance Sheet Arrangements At December 31, 2024, we were not a party to any off-balance sheet arrangements that have, or are reasonably likely to have, a current or future effect on our financial condition, changes in financial condition, revenue or expenses, results of operations, liquidity, capital expenditures or capital resources.
Off-Balance Sheet Arrangements At December 31, 2025, we were not a party to any off-balance sheet arrangements that have, or are reasonably likely to have, a current or future effect on our financial condition, changes in financial condition, revenue or expenses, results of operations, liquidity, capital expenditures or capital resources.
We believe the following policies to be critical to the judgments and estimates used in the preparation of our financial statements. 66 Revenue Recognition Our collaboration revenue includes revenue recognized for milestone payments and reimbursements under our License Agreement with Roche as well as revenue recognized under our Collaboration Agreement with BMS.
We believe the following policies to be critical to the judgments and estimates used in the preparation of our financial statements. 61 Revenue Recognition Our collaboration revenue includes revenue recognized for milestone payments and reimbursements under our License Agreement with Roche as well as revenue recognized under our Collaboration Agreement with BMS.
Contracts with Multiple Performance Obligations Significant judgment is required to apply the authoritative accounting guidance at the outset of a collaboration arrangement, and over time. Our Collaboration Agreement with BMS and our License Agreement with Roche contain multiple performance obligations.
Contracts with Multiple Performance Obligations Significant judgment is required to apply the authoritative accounting guidance at the outset of a collaboration arrangement, and over time. Our Collaboration Agreement with BMS and our License Agreement with Roche contained multiple performance obligations.
In April 2024, we renewed both leases, each for another one year term with termination dates in July 2025. Both leases have an automatic renewal clause, pursuant to which each agreement will be extended automatically for successive periods equal to their current terms, unless each agreement is cancelled by us.
In April 2025, we renewed both leases, each for another 67 one year term with termination dates in July 2026. Both leases have an automatic renewal clause, pursuant to which each agreement will be extended automatically for successive periods equal to their current terms, unless each agreement is cancelled by us.
Management’s Discussion and Analysis of Financial Condition and Results of Operations — Liquidity and Capital Resources” in our 2023 Annual Report on Form 10-K for a discussion of the cash flows for the years ended December 31, 2023 and 2022.
Management’s Discussion and Analysis of Financial Condition and Results of Operations — Liquidity and Capital Resources” in our 2024 and 2023 Annual Report on Form 10-K for a discussion of the cash flows for the years ended December 31, 2024 and 2023, respectively.
Our partnered programs include prasinezumab for the potential treatment of Parkinson’s disease and other related synucleinopathies that targets alpha-synuclein in collaboration with Roche.
These programs include prasinezumab for the potential treatment of Parkinson’s disease and other related synucleinopathies that targets alpha-synuclein in collaboration with Roche.
Other income (expense), net for the year ended December 31, 2024, was primarily foreign exchange losses from transactions with vendors denominated in euros.
Other expense, net for the year ended December 31, 2025, was primarily foreign exchange losses from transactions with vendors denominated in euros.
Our operating expenses were $289.7 million and $282.4 million for the years ended December 31, 2024, and 2023, respectively. Our research activities are aimed at developing new drug products. Our development activities involve the translation of our research into potential new drugs.
Our operating expenses were $224.3 million and $289.7 million for the years ended December 31, 2025, and 2024, respectively. Our research activities are aimed at developing new drug products. Our development activities involve the translation of our research into potential new drugs.
(3) Other R&D is comprised primarily of preclinical development and discovery programs that have not progressed to first patient dosing in a Phase 1 clinical trial and close out costs for programs that we are no longer advancing.
(2) Other R&D is comprised primarily of preclinical development and discovery programs that have not progressed to first patient dosing in a Phase 1 clinical trial, close out costs for programs that we are no longer advancing, and immaterial costs incurred on ongoing partnered programs.
Our G&A expenses primarily consist of personnel costs and related expenses, including share-based compensation and consulting expenses. Research and Development Expenses Our R&D expense increased by $1.9 million for the year ended December 31, 2024, compared to the prior year.
Our G&A expenses primarily consist of personnel costs and related expenses, including share-based compensation and consulting expenses. Research and Development Expenses Our R&D expense decreased by $87.7 million for the year ended December 31, 2025, compared to the prior year.
As of December 31, 2024, $265.3 million of our outstanding cash and cash equivalents related to U.S. operations are considered permanently reinvested. We do not intend to repatriate these funds. However, if these funds were repatriated back to Ireland, we would incur a withholding tax from the dividend distribution.
As of December 31, 2025, $232.5 million of our outstanding cash and cash equivalents related to U.S. operations are considered permanently reinveste d. We do not intend to repatriate these funds. H owever, if these funds were repatriated back to Ireland, we would incur a withholding tax from the dividend distribution.
Cash Used in Investing Activities Net cash used in investing activities w as $0.3 million for the year ended December 31, 2024, which primarily consisted of expenditures to purchase property and equipment.
Cash Used in Investing Activities Net cash used in investing activities w as $138 thousand for the year ended December 31, 2025, which consisted of expenditures to purchase property and equipment.
As of December 31, 2024, we had $471.4 million in cash a nd cash equivalents. Based on our current business plans, we believe that our existing cash and cash equivalents at December 31, 2024 are sufficient to meet our obligations for at least the next twelve months.
Based on our current business plans, we believe that our existing cash and cash equivalents at December 31, 2025 are sufficient to meet our obligations for at least the next twelve months.
Results of Operations Comparison of Years Ended December 31, 2024 and 2023 Revenue Year Ended December 31, Change 2024 2023 $ % (Dollars in thousands) Collaboration revenue $ 135,107 $ 91,320 $ 43,787 48 % Revenue from license and intellectual property 50 50 — — % Total revenue $ 135,157 $ 91,370 $ 43,787 48 % Total revenue was $135.2 million and $91.4 million for the years ended December 31, 2024, and 2023, respectively.
Results of Operations Comparison of Years Ended December 31, 2025 and 2024 Revenue Year Ended December 31, Change 2025 2024 $ % (Dollars in thousands) Collaboration revenue $ 9,634 $ 135,107 $ (125,473) (93) % Revenue from license and intellectual property 50 50 — — % Total revenue $ 9,684 $ 135,157 $ (125,473) (93) % Total revenue was $9.7 million and $135.2 million for the years ended December 31, 2025, and 2024, respectively.
Contractual Obligations Our contractual obligations as of December 31, 2024, consisted of minimum cash payments under operating leases of $12.1 million, purchase obligations of $12.7 million (of which $1.8 million is included in current liabilities), and contractual obligations under license agreements of $0.3 million (of which nil is included in current liabilities).
Contractual Obligations Our contractual obligations as of December 31, 2025, consisted of minimum cash payments under operating leases of $9.1 million, purchase obligations of $3.1 million (of which $2.7 million is included in current liabilities), obligations under our restructuring plan of $13.3 million (of which all of it is included in current liabilities), and contractual obligations under license agreements of $50 thousand.
Our R&D expenses primarily consist of personnel costs and related expenses, including share-based compensation and external costs associated with clinical activities and drug development related to our drug programs, including birtamimab, BMS-986446 ( PRX005), PRX012, PRX123, PRX019 and preclinical activities related to our discovery programs.
Our R&D expenses primarily consist of personnel costs and related expenses, including share-based compensation and external costs associated with clinical activities and drug development related to our drug programs, and preclinical activities related to our discovery programs. We also incurred wind down costs for programs that we are no longer advancing in clinical development, including birtamimab and PRX012.
Of this obligation, approximately $12.0 million remains outstanding as of December 31, 2024. 72 The following is a summary of our contractual obligations as of December 31, 2024 (in thousands): Total 2025 2026 2027 2028 Thereafter Operating leases (1) $ 12,129 $ 3,179 $ 3,158 $ 3,269 $ 2,523 $ — Purchase obligations (2) 12,729 12,633 96 — — — Contractual obligations under license agreements 274 64 60 60 45 45 Total $ 25,132 $ 15,876 $ 3,314 $ 3,329 $ 2,568 $ 45 (1) See Note 6, “ Commitments and Contingencies ” to our Consolidated Financial Statements.
Of this obligation, approximately $9.0 million remains outstanding as of December 31, 2025 The following is a summary of our contractual obligations as of December 31, 2025 (in thousands): Total 2026 2027 2028 2029 Thereafter Operating leases (1) $ 9,093 $ 3,301 $ 3,269 $ 2,523 $ — $ — Purchase obligations (2) 3,077 3,077 — — — — Obligations under the restructuring plan (3) 13,303 13,303 — — — — Contractual obligations under license agreements 50 35 15 — — — Total $ 25,523 $ 19,716 $ 3,284 $ 2,523 $ — $ — (1) See Note 6, “ Commitments and Contingencies ” to our Consolidated Financial Statements.
Cash Flows The following table summarizes, for the periods indicated, selected items in our Consolidated Statements of Cash Flows (in thousands): Year Ended December 31, 2024 2023 2022 Net cash used in operating activities $ (150,050) $ (133,906) $ (108,821) Net cash used in investing activities (298) (2,773) (464) Net cash provided by financing activities 1,554 45,103 241,457 Net increase (decrease) in cash, cash equivalents and restricted cash $ (148,794) $ (91,576) $ 132,172 71 Cash Used in Operating Activities Net cash used in operating activities was $150.1 million for the year ended December 31, 2024 , which was primarily due to ongoing research and development activities and general and administrative expenses to support those activities for a total of $289.7 million in operating expenses (adjusted to exclude non-cash charges of approximately $40.2 million) partially offset by $80.0 million option exercise payment from BMS, interest income on investments o f $25.8 million, and c ash from collection of accounts receivable of $5.2 million .
Cash Flows The following table summarizes, for the periods indicated, selected items in our Consolidated Statements of Cash Flows (in thousands): Year Ended December 31, 2025 2024 2023 Net cash used in operating activities $ (163,580) $ (150,050) $ (133,906) Net cash used in investing activities (138) (298) (2,773) Net cash provided by (used in) financing activities (139) 1,554 45,103 Net decrease in cash, cash equivalents and restricted cash $ (163,857) $ (148,794) $ (91,576) Cash Used in Operating Activities Net cash used in operating activities was $163.6 million for the year ended December 31, 2025 , which was primarily due to ongoing research and development activities, general and administrative expenses to support those activities (adjusted to exclude non-cash charges for share-based compensation expense) and payments related to our restructuring activities, partially offset by interest income on investments .
Collaboration revenue from BMS for 2023 included recognition of $91.3 million from the Tau Global License Agreement and related development services. Se e Note 7, “Significant Agreements” to the Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information.
Se e Note 7, “Significant Agreements” to the Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information.
Our ordinary shares began trading on The Nasdaq Global Market under the symbol “PRTA” on December 21, 2012, and currently trade on The Nasdaq Global Select Market.
We were formed on September 26, 2012, under the laws of Ireland and re-registered as an Irish public limited company on October 25, 2012. Our ordinary shares began trading on The Nasdaq Global Market under the symbol “PRTA” on December 21, 2012, and currently trade on The Nasdaq Global Select Market.
The increase for the year ended December 31, 2024, was primarily due to higher clinical trial expenses primarily related to the PRX012 and birtamimab programs, higher personnel expenses; offset in part by lower manufacturing expense and lower other R &D expenses.
The decrease for the year ended December 31, 2025, was primarily due to lower clinical trial expenses primarily related to PRX012 wind down, lower personnel expenses and lower manufacturing and consulting expenses.
General and Administrative Expenses Our G&A expe nses increased by $5.4 million , for the year ended December 31, 2024 , compared to the prior year primarily due to higher personnel expense. 69 Other Income (Expense) Year Ended December 31, Change 2024 2023 $ % (Dollars in thousands) Interest income $ 25,816 $ 31,014 $ (5,198) (17) % Other income (expense), net (185) (458) 273 (60) % Total other income (expense), net $ 25,631 $ 30,556 $ (4,925) (16) % Interest income decreased by $5.2 million for the year ended December 31, 2024, compared to the prior year, primarily due to lower interest income from our cash and money market accounts resulting from lower interest rates and lower cash and money market balances.
Other Income (Expense) Year Ended December 31, Change 2025 2024 $ % (Dollars in thousands) Interest income $ 14,139 $ 25,816 $ (11,677) (45) % Other expense, net (328) (185) (143) 77 % Total other income (expense), net $ 13,811 $ 25,631 $ (11,820) (46) % Interest income decreased by $11.7 million for the year ended December 31, 2025, compared to the prior year, primarily due to lower interest income from our cash and money market accounts resulting from lower interest rates and lower cash and money market balances.
(2) Purchase obligations as of the filing date includes additional $2.1 million purchase commitments to our contract manufacturers. In addition to the contractual obligations above, we also expect to have future material cash requirements related to our clinical trials, discovery and pre-clinical programs, human capital and intellectual property.
In addition to the contractual obligations above, we also expect to have future material cash requirements related to our clinical trials, discovery and pre-clinical programs, human capital and intellectual property. Assuming no significant change in our business, we expect the full year 2026 net cash used in operating and investing activities t o be approximately $50 million to $55 million.
The tax provisions for all periods presented primarily reflect U.S. federal taxes associated with recurring profits attributable to intercompany services that our U.S. subsidiary performs for the Company. No tax benefit has been recorded related to tax losses recognized in Ireland and any deferred tax assets for those losses are offset by a valuation allowance.
No tax benefit has been recorded related to tax losses recognized in Ireland or the U.S. and any deferred tax assets for those losses are offset by a valuation allowance. Comparison of the years ended December 31, 2024 and 2023 Refer to “Item 7.
Cash Provided by Financing Activities Net cash provided by financing activitie s was $1.6 million for the year ended December 31, 2024, primarily from proceeds from issuances of ordinary shares upon exercises of stock o ptions of $1.9 million. Years ended December 31, 2023 and 2022 Refer to “Item 7.
Cash Provided by (Used in) Financing Activities Net cash used in financing activitie s was $139 thousand for the year ended December 31, 2025, which consisted of expenditures related to our at-the-market offering. Years ended December 31, 2024 and 2023 Refer to “Item 7.
We are also entitled to certain potential milestone payments pursuant to our share purchase agreement with Novo Nordisk pertaining to our ATTR amyloidosis business (inclusive of coramitug, formerly PRX004). We were formed on September 26, 2012, under the laws of Ireland and re-registered as an Irish public limited company on October 25, 2012.
We are also entitled to certain potential milestone payments pursuant to our share purchase agreement with Novo Nordisk pertaining to our ATTR amyloidosis business (inclusive of coramitug, formerly PRX004). Our wholly-owned and unpartnered portfolio includes clinical and preclinical-stage programs that we are exploring strategic interest to further develop.
The following table sets forth the R&D expenses for our major programs (specifically, any active program with successful first dosing in a Phase 1 clinical trial), which were birtamimab, prasinezumab, coramitug, BMS-986446 (PRX005), PRX012, PRX019 and other R&D expenses for the years ended December 31, 2024 , and 2023 (in thousands): Year Ended December 31, 2024 2023 Birtamimab (NEOD001) $ 85,649 $ 68,831 Prasinezumab (PRX002/RG7935) 49 34 Coramitug (NNC6019/PRX004) (1) 4 91 BMS-986446 (PRX005) 264 10,063 PRX012 116,359 102,767 PRX019 (2) 5,035 7,703 Other R&D (3) 15,159 31,082 Total research and development $ 222,519 $ 220,571 (1) On July 8, 2021, we sold shares of one of our wholly-owned subsidiaries to Novo Nordisk.
The following table sets forth the R&D expenses for our major programs (specifically, programs with successful first dosing in a Phase 1 clinical trial and have material expenditures in the periods presented), which were birtamimab, PRX012, PRX019, and other R&D expenses for the years ended December 31, 2025 , and 2024 , (in thousands): Year Ended December 31, 2025 2024 Birtamimab (NEOD001) $ 53,455 $ 85,649 PRX012 54,020 116,359 PRX019 (1) 8,081 5,035 Other R&D (2) 19,296 15,476 Total research and development $ 134,852 $ 222,519 (1) R&D costs include the costs incurred from the date when PRX019 was separately tracked in preclinical development.
The decline in benefit from income taxes for the year ended December 31, 2024 , compared to the prior year, was primarily due to a lower increase in deferred tax assets related to Section 174 R&D Capitalization.
Provision for income taxes increased by $49.9 million for the year ended December 31, 2025, compared to prior year primarily due to recording a valuation allowance for the federal deferred tax assets, mainly relating to share-based compensation and R&D expenditure capitalized in previous years.
Provision for (benefit from) Income Taxes Year Ended December 31, Change 2024 2023 $ % (Dollars in thousands) Benefit from income taxes $ (6,620) $ (13,452) $ 6,832 (51) % The benefit from income taxes decreased by $6.8 million for the year ended December 31, 2024, compared to the same period in the prior year.
Provision for (benefit from) Income Taxes Year Ended December 31, Change 2025 2024 $ % (Dollars in thousands) Provision for (benefit from) income taxes $ 43,263 $ (6,620) $ 49,883 (754) % On July 4, 2025, the One Big Beautiful Bill Act (“OBBBA”) was signed into law.
Removed
Our wholly-owned programs include birtamimab for the potential treatment of AL amyloidosis, and a portfolio of programs for the potential treatment of Alzheimer’s disease including PRX012, which targets amyloid beta (Aβ), and PRX123, a novel dual Aβ-tau vaccine.
Added
Collaboration revenue from BMS was $9.6 million for the year ended December 31, 2025 , compared to $135.1 million for the year ended December 31, 2024, a decrease of $125.5 million compared to the prior year. Collaboration revenue for the year ended December 31, 2025 was related to the partial performance of our PRX019 Phase 1 Clinical Trial Obliga tion.
Removed
Collaboration revenue from BMS increased $43.8 million f or the year ended December 31, 2024 , compared to the year ended December 31, 2023.
Added
License and intellectual property revenue for the years ended December 31, 2025 and 2024, included $50,000 in each period, respectively, in license fees recognized under the License Agreement entered into on March 1, 2020, between the Company's wholly owned subsidiary, Prothen a Biosciences Limited, and F.
Removed
License and intellectual property revenue for the year ended December 31, 2024 was $50,000 compared to $50,000 f or the year ended December 31, 2023 . See Note 7, “Significant Agreements” to the Consolidated Financial Statements regarding the Novo Nordisk Share Purchase Agreement for more information.
Added
Hoffmann-La Roche Ltd. 63 Operating Expenses Year Ended December 31, Change 2025 2024 $ % (Dollars in thousands) Research and development $ 134,852 $ 222,519 $ (87,667) (39) % General and administrative 59,392 67,199 (7,807) (12) % Restructuring costs 30,080 — 30,080 nm Total operating expenses $ 224,324 $ 289,718 $ (65,394) (23) % __________ nm = not meaningful Total operating expenses consist of research and development (“R&D”) expenses, general and administrative (“G&A”) expenses, and restructuring costs .
Removed
Assuming no significant change in our business, we expect our 2025 revenue to decline over the prior year as our 2024 revenue was primarily comprised of nonrecurring revenue. 68 Operating Expenses Year Ended December 31, Change 2024 2023 $ % (Dollars in thousands) Research and development $ 222,519 $ 220,571 $ 1,948 1 % General and administrative 67,199 61,835 5,364 9 % Total operating expenses $ 289,718 $ 282,406 $ 7,312 3 % Total operating expenses consist of R&D expenses, general and administrative (“G&A”) expenses.
Added
General and Administrative Expenses Our G&A expe nses decreased by $7.8 million , for the year ended December 31, 2025 , compared to the prior year primarily due to lower personnel and consulting expenses. 64 Restructuring Costs In June 2025, we commenced a restructuring plan following our decision in May 2025 to discontinue further development of birtamimab.
Removed
In connection with the transaction, Novo Nordisk acquired our ATTR amyloidosis business, including the clinical stage antibody coramitug (PRX004). Expenses incurred relate to certain close out activities and transition services provided to Novo Nordisk. (2) R&D costs include the costs incurred from the date when PRX019 was separately tracked in preclinical development.
Added
We have incurred aggregate restructuring charges of approximately $30.1 million for the year ended December 31, 2025. Restructuring charges incurred under this plan primarily consist of employee termination benefits in connection with the reduction in force announced in June 2025 and contract termination costs.
Removed
Comparison of the years ended December 31, 2023 and 2022 Refer to “Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations” in our 2023 Annual Report on Form 10-K for a discussion of the results of operations for the year ended December 31, 2023 compared to the year ended December 31, 2022.
Added
Employee termination benefits include severance costs, employee-related benefits, and noncash share-based compensation expense related to the acceleration of the vesting of certain stock options. The vast majority of the employee termination benefits were paid out during the year ended December 31, 2025 .
Removed
This decrease in working capital during the year ended December 31, 2024 , was 70 primarily attributable to cash use of $289.7 million for operating expenses (adjusted to exclude non-cash charges) offset in part by $80.0 million option exercise payment from BMS, interest income on investments of $25.8 million , and net proceeds received from stock option exercises of approximately $1.9 million .
Added
We may also incur additional costs not currently contemplated due to events that may occur as a result of, or that are associated with, the restructuring plan. See Note 11, “Restructuring” to the Consolidated Financial Statements for more information.
Removed
Assuming no significant change in our business, we expect the full year 2025 net cash used in operating and investing activities to be approximately $168 million to $175 million.
Added
The OBBBA includes a broad range of U.S. tax reform measures, including, among other provisions, the immediate expensing of U.S. research and development expenditures. In accordance with ASC 740, the Company has recognized the effects of the new tax law in the period of enactment, and unamortized Section 174 balances will be recognized over the remaining amortization period.
Added
As the Company maintains a full valuation allowance on its deferred tax assets, the legislation did not have a material impact on our consolidated financial statements for the year ended December 31, 2025.
Added
This decrease in working capital during the year ended December 31, 2025, was primarily attributable to ca sh used in operating activities of $163.6 million . As of December 31, 2025, we had $307.5 million in cash a nd cash equivalents.
Added
(2) As of the filing date, there were no material changes to our Purchase obligations subsequent to December 31, 2025 (3) Includes cash obligations under our restructuring plan. For additional information, see Note 11, “Restructuring” to our Consolidated Financial Statements.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

4 edited+1 added−1 removed4 unchanged
Biggest changeCredit Risk Financial instruments that potentially subject us to concentration of credit risk consist of cash and cash equivalents and accounts receivable. We place our cash and cash equivalents with high credit quality financial institutions and pursuant to our investment policy, we limit the amount of credit exposure with any one financial institution.
Biggest changeWe place our cash and cash equivalents with high credit quality financial institutions and pursuant to our investment policy, we limit the amount of credit exposure with any one financial institution. Deposits held with banks have exceeded, and will continue to exceed, federally insured limits on such deposits.
Foreign Currency Risk Our business is primarily conducted in U.S. dollars except for our agreements with contract manufacturers for drug supplies wh ich are primarily denominated in euros. We recor ded losses on foreign currency exchange rate differences of approximately $185,000, $458,000 and $397,000 during the years ended December 31, 2024, 2023 and 2022, respectively.
Foreign Currency Risk Our business is primarily conducted in U.S. dollars except for our agreements with contract manufacturers for drug supplies wh ich are primarily denominated in euros. We recor ded losses on foreign currency exchange rate differences of approximately $328,000, $185,000 and $458,000 during the years ended December 31, 2025, 2024 and 2023, respectively.
Deposits held with banks have exceeded, and will continue to exceed, federally insured limits on such deposits. We are exposed to credit risk in the event of a default by the financial institutions holding our cash and cash equivalents. We have not experienced any losses on our deposits of cash and cash equivalents.
We are exposed to credit risk in the event of a default by the financial institutions holding our cash and cash equivalents. We have not experienced any losses on our deposits of cash and cash equivalents. Our credit risk exposure is up to the extent recorded on the Company's Consolidated Balance Sheets. 69
The primary objectives of our investment policy are to preserve principal and maintain proper liquidity to meet our operating requirements. Our investment policy also specifies credit quality standards for our investments and limits the amount of credit exposure to any single issue, issuer or type of investment.
The primary objectives of our investment policy are to preserve principal and maintain proper liquidity to meet our operating requirements.
Removed
Our credit risk exposure is up to the extent recorded on the Company's Consolidated Balance Sheets. 73
Added
Our investment policy also specifies credit quality standards for our investments and limits the amount of credit exposure to any single issue, issuer or type of investment. 68 Credit Risk Financial instruments that potentially subject us to concentration of credit risk consist of cash and cash equivalents.

Other PRTA 10-K year-over-year comparisons