Prothena Announces Corporate Restructuring

Prothena Corporation plc (NASDAQ: PRTA) today announced that the Company has initiated an approximate 63% reduction in its workforce to substantially reduce its operating costs to those necessary to support its remaining wholly owned programs, its obligations to partnered programs, and its anticipated business development activities.

“We have incredible Prothenians who are among the industry’s most talented professionals and have dedicated their careers to advancing new treatments for patients,” said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. “I want to express my sincere gratitude to each Prothenian being affected by today’s announcement and thank them for their passion toward our mission to treat diseases caused by protein dysregulation.”

The board, management, and Company’s financial advisors are collectively evaluating a comprehensive range of business options to best serve the interest of its shareholders that consider the implications of multiple recent and upcoming milestones, including:

• Earlier this week Roche announced that it will advance prasinezumab into Phase 3 development for early-stage Parkinson’s disease
• Company expects initial data in August from Phase 1 ASCENT clinical trials of its wholly owned PRX012 program in Alzheimer’s disease
• Novo Nordisk expects to share data from its Phase 2 clinical trial evaluating coramitug for ATTR-CM in the second half of 2025
• Company expects to complete a Phase 1 clinical trial for PRX019 in collaboration with Bristol Myers Squibb in 2026
• Bristol Myers Squibb expects to complete a Phase 2 TargetTau-1 clinical trial evaluating BMS-986446 in Alzheimer’s disease in 2027
• Company has potential to receive up to $105 million in 2026 for clinical milestones from various partnered programs.

Revised 2025 Financial Guidance

Based on this reorganization, the Company is revising its full year 2025 financial guidance and expects its 2025 net cash burn from operating and investing activities to be $170 to $178 million and to end the year with approximately $298 million (midpoint) in cash, cash equivalents, and restricted cash. The estimated 2025 net cash burn from operating and investing activities is primarily driven by an estimated net loss of $240 to $248 million, which includes an estimated $36 million of non-cash share-based compensation expense and a $45 million non-cash income tax expense to book a full valuation allowance against its U.S. deferred tax assets. The estimated 2025 net loss includes $105 to $110 million of operating expenses associated with birtamimab and the Company's reorganization, including research, development, manufacturing and pre-commercial expenses, severance costs and contract termination fees related to manufacturing obligations, and approximately $12 million of non-cash share-based compensation expense. Therefore, the Company expects the discontinuation of birtamimab development will result in an approximate decrease of $96 million (midpoint) in annualized net cash burn.

Please see the form 8-K the Company filed today for additional financial and other details.

About Prothena

Prothena Corporation plc is a clinical-stage 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. Fueled by its deep scientific expertise built over decades of research, Prothena 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. Prothena’s pipeline includes both wholly owned and partnered programs being developed for the potential treatment of diseases including ATTR amyloidosis with cardiomyopathy, Alzheimer’s disease, Parkinson’s disease and a number of other neurodegenerative diseases. For more information, please visit the Company’s website at www.prothena.com and follow the Company on X (formerly Twitter) @ProthenaCorp.

Forward-Looking Statements

This press release contains forward-looking statements. These statements relate to, among other things, the sufficiency of our cash position to fund completion of our ongoing clinical trials; expected milestones in 2025, 2026, and beyond, including upcoming initial data from the Phase 1 ASCENT clinical trials on PRX012 in Alzheimer’s disease expected in August 2025, and program updates from our partners at Novo Nordisk expected in the second half of 2025, and Bristol Myers Squibb expected in 2026; the estimates of expenses associated with the reduction in workforce prove inaccurate; we incur greater than estimated expenses in connection with the reduction in workforce; our business, financial condition or operating results are adversely affected by the reduction in workforce; our anticipated net cash burn from operating and investing activities for 2025 and expected cash balance at the end of 2025; and our estimated net loss and non-cash share-based compensation expense for 2025; and our continuing evaluation of business options. These statements are based on estimates, projections and assumptions that may prove not to be accurate, and actual results could differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, including but not limited to uncertainties related to the completion of operational and financial closing procedures, audit adjustments and other developments that may arise that would require adjustments to the preliminary financial results included in this press release, as well as those described in the “Risk Factors” sections of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 8, 2025, and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. We undertake no obligation to update publicly any forward-looking statements contained in this press release as a result of new information, future events, or changes in our expectations.

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