Prothena : Corporate Overview

CORPORATE OVERVIEW

August 2023

Forward-Looking Statements

This overview contains forward-looking statements. These statements relate to, among other things, the sufficiency of our cash position to fund advancement of a broad pipeline; the continued advancement of our discovery, preclinical, and clinical pipeline, and expected milestones in 2023, 2024, and beyond; our goal to continue building a biology-directed engine targeting protein dysregulation; our potential to advance, initiate, and complete IND enabling studies for our discovery and preclinical programs; the treatment potential, designs, proposed mechanisms of action, and potential administration of birtamimab, prasinezumab, NNC6019 (formerly PRX004), PRX005, PRX012, and PRX123; potential indications and attributes of epitopes and antibodies we have identified in our programs; plans for ongoing and future clinical studies of birtamimab, prasinezumab, NNC6019, PRX005, PRX012, and PRX123 (including the filing of an IND application); the expected timing of reporting data from clinical studies of birtamimab, prasinezumab, NNC6019, and PRX012; and amounts we might receive under our partnerships and collaborations with Roche, BMS, and 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 Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 3, 2023 and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. This overview is made as of August 3, 2023, and 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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Our Mission Today

We are Focused on Delivering Life-Saving Therapies…

…for unmet medical needs caused by

diseases of protein dysregulation

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We are Addressing Devastating Proteinopathies Affecting Millions of Patients and Families Worldwide

NEUROSCIENCE

RARE PERIPHERAL AMYLOID DISEASES

Alzheimer's

disease (AD)

55 million

People worldwide living with Alzheimer's disease or other dementias1

7th

Leading cause of death in United States5

$1 trillion

In annual US healthcare costs by 2050 from AD and other dementias7

Parkinson's

disease (PD)

10 million

People living with PD worldwide2

Fastest increasing

Neurodegenerative disease6

$52 billion

In overall economic burden in the US8

Amyloid light chain amyloidosis (AL)

60,000-120,000

Patients with Mayo Stage IV AL amyloidosis globally3

5.8 months

Median overall survival in Mayo Stage IV patients with AL amyloidosis

Transthyretin amyloidosis (ATTR)

450,000

Estimated number of patients worldwide with wtATTR or ATTRv4

2.08 years

Median overall survival New York Heart Association class

1. patients with ATTR cardiomyopathy9

1 Alzheimer's Disease International. Dementia Statistics, 2 Parkinson's Foundation. Understanding Parkinson's. Statistics, 3 Kyle et al Mayo Clin Proc, 2019, 4 Gonzalez-Lopez et al, 2017; Mauer et al, 2016; Gagliardi et al, 2018, 5 2021 Alzheimer's Disease

Fact Sheet, National Institute on Aging, NIH, 6 GBD 2015 Neurological Disorders Collaborator Group (2017) Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study

2015. Lancet Neurol 16, 877-897,7 Alzheimer's Association Facts and Figures Report 2022, 8 The Economic Burden of Parkinson's Disease - The Michael J. Fox Foundation, 9 Kumar et al 2012, Pinney J et al. 2013; Gonzalez-Lopez E et al. 2017

4	wtATTR: Wild-Type ATTR
ATTRv: Hereditary amyloid transthyretin

Our Team has Pioneered Multiple Scientific

Advances in Protein Dysregulation

OUR LEGACY INCLUDES FOUNDATIONAL DISCOVERIES IN THE UNDERSTANDING OF ALZHEIMER'S DISEASE

1986

Athena Neurosciences founded

1996

Athena acquired by Elan

2012

Prothena spins-out

from Elan with a wholly-owned drug discovery platform

Pioneered fundamental discoveries elucidating the roles of beta amyloid (Aβ), gamma secretase and beta secretase play in disease1

First to show that anti-Aβ immunotherapy prevented and cleared amyloid plaques in the brains of transgenic mice2

First to demonstrate plaque clearance by an n-terminusantibody in brains from AD patients3

Discovered biological cause of ARIA and vascular recovery following anti-Aβ immunotherapy4

Developed PRX012, best-in-classanti-Aβ product candidate, with ~10X greater binding potency to fibrillar Aβ vs. aducanumab5 and ~20X greater binding potency against protofibrils vs. lecanemab6

	1 Games, D., Adams, D., Alessandrini, R. et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. 1995 Nature; 2 Schenk, D., Barbour, R., Dunn, W. et al. Immunization with amyloid-β
	attenuates Alzheimer-disease-like pathology in the PDAPP mouse. 1999 Nature; 3 Rinne et al, C-BiP PET assessment of change in fibrillar amyloid-b load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind,
5	placebo-controlled, ascending -dose study, 2010, 4 Zago W, Schroeter S, Guido T, et al. Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities. 2013 Alzheimers Dement.
5 PRX012 Induces Microglia-Mediated Clearance of Pyroglutamate-Modified and -Unmodified Aß in Alzheimer's Disease Brain Tissue presented at AAIC 2021; 6 Binding Characteristics of Surrogate PRX012 Demonstrate Potent Engagement of

Toxic Abeta Protofibrils and Robust Clearance of Pyroglutamate-Modified Abeta presented at AD/PD 2023