Here are 1-3 brief analogies for Prothena:

• Prothena is like a Biogen or Eli Lilly, but intensely focused on developing antibody therapies for neurodegenerative diseases like Alzheimer's and Parkinson's.
• Think of Prothena as a specialized biotech company like Biogen or Eli Lilly, dedicated to finding novel immunotherapies for devastating neurodegenerative and amyloid diseases.
• A biotech akin to Biogen or Eli Lilly, but with a laser focus on developing treatments that clear the misfolded proteins driving diseases like Alzheimer's and Parkinson's.

• Birtamimab: An investigational antibody designed to clear amyloid fibrils in patients with AL amyloidosis, currently in a Phase 3 clinical trial.
• PRX012: An investigational antibody targeting amyloid-beta (Aβ) for the potential treatment of Alzheimer's disease, currently in a Phase 1 clinical trial.
• PRX005 (co-developed with Roche): An investigational antibody targeting alpha-synuclein for the treatment of Parkinson's disease, currently in a Phase 2 clinical trial.
• PRX004 (licensed to Novo Nordisk): An investigational antibody targeting transthyretin (TTR) for the treatment of ATTR amyloidosis, currently in a Phase 2 clinical trial.

Prothena (PRTA) is a biotechnology company that primarily sells to other companies, specifically larger pharmaceutical companies, through collaboration and licensing agreements for its therapeutic candidates.

Based on its most recent financial disclosures (fiscal year 2023), its major customer was:

• Bristol Myers Squibb (Symbol: BMS)

Historically, another significant customer and collaborator was:

• Roche Holding AG (Symbol: RHHBY - for American Depositary Receipts) - While a major partner for several years and contributing substantially to Prothena's revenue, the collaboration agreement for prasinezumab was terminated by Roche in late 2023.

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Gene G. Kinney, Ph.D. President and Chief Executive Officer

Dr. Gene G. Kinney has served as President and Chief Executive Officer of Prothena since 2016, and he has been a member of the company's Board of Directors since September 2016. He was a founding member of Prothena's leadership team, initially serving as Chief Scientific Officer and Head of Research and Development from 2012 to 2016, and then as Chief Operating Officer for part of 2016. Before joining Prothena, Dr. Kinney held various positions at Elan Pharmaceuticals Inc. from 2009 to 2012, including Vice President of Pharmacology and Senior Vice President of Pharmacological Sciences, where he also served as Head of Nonclinical Research for Janssen Alzheimer Immunotherapy R&D. Prior to that, from 2001 to 2009, he was Senior Director, Head of Central Pharmacology at Merck Research Laboratories. He also held positions at Bristol Myers Squibb and was an Assistant Professor at Emory University School of Medicine. Dr. Kinney also serves as Chairman at Libra Therapeutics, Inc.

Tran B. Nguyen Chief Strategy Officer and Chief Financial Officer

Mr. Tran B. Nguyen has served as Chief Strategy Officer since September 2021 and Chief Financial Officer since 2013. He also served as Chief Operating Officer from June 2018 to September 2021. Mr. Nguyen brings over 25 years of finance experience from the biotechnology, banking, and private equity industries. Before joining Prothena in 2013, he was Chief Financial Officer at Somaxon Pharmaceuticals, Inc. until its sale in 2013. Previously, Mr. Nguyen served as Vice President and Chief Financial Officer at Metabasis Therapeutics, Inc. until its sale in 2010. His background also includes roles as Vice President in the Healthcare Investment Banking group at Citi Global Markets, Inc. (2007-2009) and various healthcare investment banking capacities at Lehman Brothers, Inc. (2004-2007). Mr. Nguyen has also served on the board of directors for Sierra Oncology, Inc. and Rain Therapeutics Inc.

Brandon Smith Chief Operating Officer

Mr. Brandon Smith has served as Chief Operating Officer of Prothena since September 2021. Prior to this, he was the Chief Business Officer from March 2020 through September 2021. Before joining Prothena in 2020, Mr. Smith was the Chief Operating Officer at Iconic Therapeutics, Inc., a biopharmaceutical company, from 2017 to 2020. From 2012 to 2017, he held senior leadership positions at Impax Laboratories, LLC, including Senior Vice President and Vice President of Corporate Development and Strategy. Mr. Smith also spent seven years at Amgen Inc. (2005-2012) in roles such as Executive Director, Biosimilars Strategy, and Director, Strategy and Corporate Development. He began his career as a Consultant and Project Leader at The Boston Consulting Group.

Chad J. Swanson, Ph.D. Chief Development Officer

Dr. Chad J. Swanson was appointed Chief Development Officer in September 2024, after joining Prothena in January 2023 as Senior Vice President and Head of Clinical Development. He is a neuropharmacologist with over two decades of industry experience. Prior to Prothena, Dr. Swanson served as Executive Director of Clinical Research in the Alzheimer's Disease Brain Health group at Eisai, Inc. During his 11-year tenure at Eisai, he was the International Project Team Leader responsible for the lecanemab program, where he successfully delivered a Phase 2 dose-finding study that established proof of concept for the treatment of early Alzheimer's disease.

Key Risks to Prothena (PRTA)

1. Clinical Trial Failures and Pipeline Dependence: As a late-stage clinical biotechnology company, Prothena's business success is heavily dependent on the successful development and approval of its investigational therapies. The discontinuation of its lead candidate, birtamimab, following a Phase 3 trial failure, underscores this significant risk. This has led to a narrowed pipeline and increased reliance on the success of other candidates, such as PRX012 for Alzheimer's disease and prasinezumab for Parkinson's disease. The development of treatments for neurodegenerative diseases like Alzheimer's is particularly challenging, with a historically high failure rate in clinical trials, posing substantial clinical and regulatory risks for Prothena's future prospects.
2. Unprofitability and Need for Additional Capital: Prothena is currently an unprofitable company with negative free cash flow, typical for a biotechnology firm in its development phase. While the company has reported a strong cash position, it anticipates requiring additional capital to fund ongoing research and development, and eventual commercialization of its drug candidates. Its financial trajectory hinges on clinical validation and operational execution, and the significant investment in R&D means a continued reliance on external funding or successful partnerships to sustain operations.
3. Partnership and Regulatory Risks: Prothena's pipeline includes both wholly-owned and partnered programs, with collaborations such as the one with Roche for prasinezumab. There is an inherent risk that a partner could choose to terminate a collaboration at any time, which would significantly impact Prothena's resources and development timelines. Furthermore, advancing drug candidates requires navigating complex regulatory landscapes, and there is no guarantee that regulatory authorities, such as the FDA, will allow drugs to proceed through clinical stages or grant marketing approvals.

The success and market entry of anti-amyloid antibodies like Leqembi (lecanemab) from Eisai/Biogen and Donanemab from Eli Lilly in treating early Alzheimer's disease present a clear emerging threat to Prothena's PRX012 program. These approved and near-approved therapies are rapidly establishing a new standard of care for amyloid-targeting treatments in Alzheimer's disease. As PRX012 is still in Phase 1 development, it faces the challenge of demonstrating significantly superior efficacy, safety, or administration convenience to effectively compete against these validated and commercially available treatments that are setting the new market benchmark.

Prothena (PRTA) is a clinical-stage biotechnology company focused on developing novel therapies for neurodegenerative and rare peripheral amyloid diseases. The addressable market sizes for their main product candidates and programs are detailed below:

Parkinson's Disease (Prasinezumab - PRX002)

Prothena is evaluating prasinezumab, a humanized monoclonal antibody, in collaboration with Roche for the treatment of Parkinson's disease and other related synucleinopathies. Roche anticipates peak sales potential exceeding $3.5 billion (unadjusted) for prasinezumab.

• Global Market: The global Parkinson's Disease Drugs Market is projected to reach USD 5.76 billion in 2025 and grow to USD 6.87 billion by 2030. Other estimates place the global Parkinson's disease therapeutics market at USD 6.59 billion in 2024, increasing to approximately USD 13.34 billion by 2034. The market is also expected to grow from USD 6.42 billion in 2024 to approximately US$ 11.28 billion by 2034.
• U.S. Market: The U.S. Parkinson's disease therapeutics market was valued at USD 2.15 billion in 2024 and is predicted to be worth around USD 4.25 billion by 2034.

ATTR Amyloidosis (Coramitug - formerly PRX004)

Prothena's former candidate, Coramitug (PRX004), for ATTR amyloidosis, is now fully licensed to Novo Nordisk, with Prothena eligible for royalties. Novo Nordisk expects to advance Coramitug into a Phase III program for ATTR amyloidosis with cardiomyopathy (ATTR-CM) in 2025.

• Global Market: The global ATTR amyloidosis treatment market is estimated to be valued at USD 4.14 billion in 2025 and is expected to reach USD 7.52 billion by 2032. Another report values the global transthyretin amyloidosis treatment market at USD 6.94 billion in 2024, with a projection to reach USD 20.35 billion by 2033. The transthyretin amyloidosis treatment market size is estimated at USD 6.12 billion in 2025, and is expected to reach USD 12.52 billion by 2030.
• Regional Market: North America holds the largest market share for transthyretin amyloidosis treatment, at 46.3% in 2024. The United States accounted for the highest hereditary transthyretin amyloidosis treatment market size in the top 7 markets (US, EU4, UK, and Japan) in 2024.

Alzheimer's Disease (PRX012, PRX123, PRX019)

Prothena is heavily focused on its Alzheimer's disease pipeline, particularly PRX012, an experimental Alzheimer's therapy targeting amyloid beta, which analysts assign a 30% probability of success and potential approval by 2027. PRX012 has a potential for multi-billion-dollar peak sales. The company also has PRX123 (a dual Aβ and Tau vaccine) and PRX019 (an anti-Tau antibody) in its pipeline for Alzheimer's and neurodegenerative diseases.

• Global Market: The global Alzheimer's drug market size is calculated at USD 4.18 billion in 2025 and is forecasted to reach approximately USD 7.13 billion by 2034. The global Alzheimer's therapeutics market size was valued at USD 5.8 billion in 2023 and is expected to exhibit growth at a CAGR of 9.8% from 2024 to 2032. The Alzheimer's disease market is expected to grow from $2.4 billion in 2023 to $19.3 billion by 2033 across the eight major markets (US, France, Germany, Italy, Spain, UK, Japan, and China).
• U.S. Market: The North American Alzheimer's drug market is expected to dominate, holding a 47% share in 2024. The U.S. Alzheimer's drug market size was USD 1.48 billion in 2024 and is projected to be around USD 2.73 billion by 2034.

AL Amyloidosis (Birtamimab)

Prothena discontinued the development of birtamimab for AL amyloidosis following disappointing Phase 3 results in August 2025.

• Global Market (for context, as the program is discontinued): The global AL amyloidosis market size was valued at $3.11 billion in 2024, projected to reach $3.52 billion in 2025, and grow to $5.74 billion by 2029. Other estimates include a global AL amyloidosis therapeutics market value of USD 2.59 billion in 2025, reaching USD 5.24 billion by 2035.
• Regional Market (for context): The AL amyloidosis market across the top 7 markets (US, EU4, UK, and Japan) reached USD 3,816.6 Million in 2024 and is expected to reach USD 15,003.3 Million by 2035.

Prothena (PRTA) is poised for potential revenue growth over the next 2-3 years, primarily driven by the advancement of its diversified and partnered clinical pipeline. Key drivers include significant milestone payments and future royalties from its collaborations with major pharmaceutical companies.

1. Advancement of Prasinezumab with Roche for Parkinson's Disease: Roche, Prothena's partner, is expected to initiate the late-stage PARAISO study for prasinezumab in early-stage Parkinson's disease by the end of 2025. This collaboration has a reported peak sales potential exceeding $3.5 billion, and successful progression will trigger milestone payments and future royalties for Prothena.

2. Progression of Coramitug (formerly PRX004) with Novo Nordisk for ATTR Amyloidosis: Novo Nordisk acquired Coramitug and has initiated the late-stage CLEOPATTRA study for ATTR amyloidosis with cardiomyopathy. Prothena anticipates earning a clinical milestone payment when specific enrollment criteria are met in this ongoing Phase 3 study.

3. Milestone Payments and Royalties from Bristol Myers Squibb Partnerships: Prothena's collaboration with Bristol Myers Squibb (BMS) for neurodegenerative diseases represents a significant revenue driver. This includes BMS-986446 (formerly PRX005), an antibody targeting tau for Alzheimer's disease, which received Fast Track Designation from the FDA in October 2025 and is in a Phase 2 trial. Additionally, Prothena initiated a Phase 1 clinical trial for PRX019 for neurodegeneration in 2025, with a clinical milestone expected by the end of 2026 if BMS decides to develop it further.

4. Potential New Partnerships and Out-licensing of Wholly-Owned Programs: Prothena aims to generate revenue through strategic partnerships and out-licensing of its wholly-owned pipeline assets. For example, the company plans to explore partnership interest to further develop PRX012 and its preclinical PRX012-TfR antibody for Alzheimer's disease. Successful execution of such partnerships would bring in upfront payments, milestone payments, and potential royalties.

Share Repurchases

• Prothena is convening an Extraordinary General Meeting (EGM) on November 19, 2025, to seek shareholder approval for a reduction in share capital to create distributable reserves.
• This capital reduction is intended to support a potential share redemption program in 2026, if deemed appropriate by the Board of Directors.

Share Issuance

• As of October 31, 2025, Prothena had approximately 53.8 million ordinary shares outstanding.
• The company projects approximately $41 million in non-cash share-based compensation expense for the full year 2025.
• Shareholders authorized the Board in May 2022 to issue ordinary shares up to the amount of authorized share capital and to opt out of the statutory pre-emption right for such issuances.

Inbound Investments

• Bristol Myers Squibb obtained an exclusive global license for PRX019 for $80 million, with Prothena eligible for up to $617.5 million in additional milestone payments and tiered royalties.
• Novo Nordisk acquired Prothena's ATTR amyloidosis business and pipeline, including Coramitug (PRX004), for up to $1.2 billion.
• Prothena is eligible to earn up to $105 million in aggregate clinical milestone payments by the end of 2026 related to the advancement of coramitug by Novo Nordisk and PRX019 by Bristol Myers Squibb.

Capital Expenditures

• Prothena's historical capital expenditures were $0 million in 2020, $1 million in 2021, $0 million in 2022, $3 million in 2023, and $0 million in 2024.
• Projected capital expenditures are $5 million for 2025, $6 million for 2026, $8 million for 2027, $10 million for 2028, and $12 million for 2029.
• The estimated full year 2025 net cash used in operating and investing activities is expected to be $170 million to $178 million, primarily driven by R&D investments.