Prothena Announces Achievement of $50 Million Clinical Milestone Payment from Novo Nordisk Related to Ongoing Phase 3 Clinical Trial for Coramitug (Formerly PRX004) in ATTR Amyloidosis with Cardiomyopathy

• Coramitug is a potential first-in-class amyloid depleter antibody for the treatment of ATTR amyloidosis with cardiomyopathy 1-3

• Prothena has now earned $150 million to date of the $1.2 billion total eligible milestone payments from Novo Nordisk

DUBLIN--(BUSINESS WIRE)-- Prothena Corporation plc (NASDAQ:PRTA) today announced that the Company earned a $50 million milestone payment from Novo Nordisk related to the achievement of a prespecified enrollment target in the ongoing Phase 3 CLEOPATTRA clinical trial evaluating coramitug (formerly PRX004), a potential first-in-class amyloid depleter antibody, for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM).

Novo Nordisk is evaluating coramitug in the ongoing Phase 3 CLEOPATTRA clinical trial in approximately 1280 participants with ATTR-CM with primary completion expected in 2029 ( NCT07207811 ).

Novo Nordisk gained full worldwide rights to the intellectual property and related rights of the ATTR amyloidosis business and pipeline it acquired from Prothena in July 2021. Under the terms of the acquisition agreement, Prothena is eligible to receive up to $1.2 billion upon achievement of clinical development and sales milestones, including $150 million earned to date.

About Coramitug (formerly PRX004)

Coramitug (formerly PRX004) 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 1-3 . Coramitug’s proposed mechanism of action is to deplete both the deposited amyloid to improve organ function and circulating non-native TTR to prevent further organ deposition 1-3 . This differentiated depleter mechanism of action could be developed as a monotherapy approach to ATTR amyloidosis and might also complement existing therapeutic approaches which either stabilize or reduce production of the native TTR tetramer 3 .

In a Phase 2 clinical trial conducted by Novo Nordisk, coramitug 60 mg/kg significantly reduced NT-proBNP in a patient population predominantly in which the vast majority (>80%) were already receiving standard of care treatment for ATTR-CM. Furthermore, compared with placebo, coramitug was associated with improvements in multiple echocardiographic parameters of cardiac function, and was well-tolerated in participants with ATTR-CM. These findings support the potential of coramitug as an amyloid-clearing immunotherapy for ATTR-CM and provide a rationale for additional clinical investigation of coramitug for the treatment of patients with ATTR-CM 4 .

About Prothena

Prothena Corporation plc 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. 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 Parkinson’s disease, ATTR amyloidosis with cardiomyopathy, Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS) and a number of other neurodegenerative diseases. Prothena is developing and applying its proprietary CYTOPE ® technology to target a broad spectrum of intracellular disease pathways in the brain and periphery. 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 treatment potential, design, and proposed mechanism of action coramitug; plans for ongoing and future clinical trials of coramitug; and amounts we might receive under our agreement with Novo Nordisk. 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 those described in the “Risk Factors” sections of our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 27, 2026, 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.

References:

1 Preclinical studies of PRX004 (coramitug) – data on file 2 Higaki JN et al. Amyloid , 2016 3 Suhr OB et al. Amyloid , 2025 4 Fontana M et al. Circulation , 2025

Mark Johnson, CFA Senior Vice President, Head of Investor Relations and Corporate Communications 650-837-8550 IR@prothena.com Media@prothena.com

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