Business Overview and History
Prothena Corporation plc (PRTA) is a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on its deep expertise in protein dysregulation. The company's mission is to create transformative therapies addressing significant unmet medical needs for the millions of patients affected by devastating life-threatening diseases caused by protein misfolding and aggregation.
Prothena Corporation plc was formed on September 26, 2012 under the laws of Ireland and re-registered as an Irish public limited company on October 25, 2012. The company's 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. As part of the spin-out from Elan Corporation, plc, Prothena entered into several agreements with Elan, including an Amended and Restated Intellectual Property License and Contribution Agreement and a Tax Matters Agreement, which set the framework for Prothena's initial relationship with Elan.
In December 2013, Prothena expanded its portfolio through a License, Development, and Commercialization Agreement with Roche to develop and commercialize certain antibodies targeting alpha-synuclein, including prasinezumab, for the potential treatment of Parkinson's disease and other related synucleinopathies. This agreement made Roche primarily responsible for developing, obtaining and maintaining regulatory approval for, and commercializing the licensed products.
Further broadening its collaborative efforts, Prothena entered into a Collaboration Agreement with Celgene (later acquired by Bristol Myers Squibb) in March 2018 to develop and commercialize antibodies targeting tau, TDP-43 and an undisclosed target. This agreement provided Celgene with options to exclusively license rights to these programs.
The company faced a significant setback in 2017 when it halted development of its NEOD001 program for AL amyloidosis after it failed to meet the primary endpoint in a Phase 3 clinical trial. This challenge resulted in a substantial financial impact and workforce reduction for Prothena. However, the company has persevered, continuing to advance its pipeline of investigational therapies and maintaining its focus on protein dysregulation expertise.
Financial Performance and Strength
Prothena's financial position remains robust, with a strong cash and cash equivalents balance of $471.4 million as of December 31, 2024. The company reported net cash used in operating and investing activities of $150.3 million for the full year 2024, at the low end of its guidance range of $148 million to $160 million.
For the full year 2024, Prothena reported total revenue of $135.2 million, of which $135.1 million was collaboration revenue and $50,000 was revenue from license and intellectual property. The company's total operating expenses for the year were $289.7 million, with research and development expenses of $222.5 million and general and administrative expenses of $67.2 million. Prothena reported a net loss of $122.3 million for the year ended December 31, 2024, also at the low end of its guidance range of $120 million to $135 million.
In the most recent quarter (Q4 2024), Prothena reported revenue of $2.1 million and a net loss of $58 million. Revenue decreased 85% year-over-year, primarily due to a decline in collaboration revenue.
The company's financial strength is further evidenced by its strong liquidity position, with a current ratio and quick ratio of 10.01. Prothena maintains a zero-debt balance sheet, with a debt-to-equity ratio of just 0.02, providing it with ample resources to advance its clinical pipeline.
Looking ahead to 2025, Prothena expects net cash used in operating and investing activities to be between $168 million and $175 million, with an estimated net loss of $197 million to $205 million, including $41 million in non-cash share-based compensation expense. The company anticipates ending 2025 with approximately $301 million in cash, cash equivalents, and restricted cash.
Transformative Pipeline and Upcoming Milestones
Prothena's pipeline is anchored by several programs that have the potential to transform the treatment landscape for their respective indications. The company's lead wholly-owned program, birtamimab, is currently in a confirmatory Phase 3 AFFIRM-AL clinical trial for the treatment of AL amyloidosis.
Birtamimab is an investigational humanized antibody that targets toxic misfolded light chain proteins, which can accumulate and cause organ dysfunction and failure in patients with AL amyloidosis. The AFFIRM-AL trial is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA, where statistical significance and success are defined at a p-value equal to or less than 0.10 on the primary endpoint of time to all-cause mortality. Topline results from this trial are expected in the second quarter of 2025. If positive, Prothena plans to submit a Biologics License Application (BLA) to the FDA for potential U.S. launch in the second half of 2026. Birtamimab has been granted Fast Track Designation by the FDA and Orphan Drug Designation by both the FDA and EMA for the treatment of AL amyloidosis.
In Alzheimer's disease, Prothena's PRX012 is a potential best-in-class anti-Aβ antibody designed for a once-monthly subcutaneous administration, addressing the unmet need for a treatment option that can improve patient convenience and access. PRX012 is an investigational antibody that targets amyloid beta (Aβ), a protein implicated in Alzheimer's disease. The company has advanced PRX012 into a Phase 1 clinical trial to evaluate its safety, tolerability, immunogenicity, and pharmacokinetics. PRX012 has been granted Fast Track Designation by the FDA for the treatment of Alzheimer's disease. Prothena expects to report multiple clinical readouts from the ongoing Phase 1 ASCENT trials for PRX012 starting in mid-2025 and continuing throughout the year.
Additionally, Prothena's PRX123 dual Aβ-tau vaccine has been granted Fast Track designation by the FDA and is advancing through clinical development, leveraging the company's expertise in targeting key epitopes within amyloid-beta and tau proteins. PRX123 is a dual vaccine being developed by Prothena that concomitantly targets key epitopes within both the Aβ and tau proteins for the potential prevention and treatment of Alzheimer's disease. Prothena recently initiated a Phase 1 clinical trial for PRX123 after receiving IND clearance and Fast Track Designation from the FDA.
Prothena's partnered programs also hold significant promise. The Phase 2b PADOVA study of prasinezumab in early Parkinson's disease, conducted by partner Roche, showed potential clinical effect in the primary endpoint, with more pronounced effects in the subgroup of patients on levodopa therapy. Roche is continuing to evaluate the data and determine next steps.
In collaboration with Bristol Myers Squibb, Prothena's programs include BMS-986446, a potential best-in-class anti-tau antibody for Alzheimer's disease, and PRX019 for the treatment of neurodegenerative diseases, both of which are advancing through clinical development.
Risks and Challenges
As a clinical-stage biotechnology company, Prothena faces inherent risks associated with the drug development process. Successful completion of clinical trials, regulatory approvals, and commercialization of its drug candidates are not guaranteed, and any delays or failures could significantly impact the company's financial performance and growth prospects.
Additionally, Prothena's reliance on strategic partnerships, such as with Roche and Bristol Myers Squibb, introduces risks related to the successful execution of these collaborations, including the potential for disagreements, changes in priorities, or termination of agreements.
The company also operates in a highly competitive landscape, with other biotechnology and pharmaceutical companies pursuing similar therapeutic targets and modalities. Prothena's ability to maintain its competitive edge and secure market share for its approved products will be crucial to its long-term success.
Conclusion
Prothena's robust pipeline of investigational therapies, built on its deep expertise in protein dysregulation, positions the company as a biotechnology powerhouse poised to drive transformative changes in the treatment of devastating neurodegenerative and rare peripheral amyloid diseases. With several key milestones on the horizon, including the pivotal Phase 3 AFFIRM-AL trial for birtamimab and anticipated data readouts for its Alzheimer's disease programs, Prothena is well-equipped to capitalize on its scientific knowledge and create long-term value for shareholders. The company's strong financial position, with a substantial cash balance and zero-debt balance sheet, provides a solid foundation for advancing its clinical pipeline and pursuing its mission to develop novel therapies for patients in need.