Prothena : Corporate Overview

Corporate Overview

January 2022

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 2022 and beyond; our goal to continue building a biology-directed discovery engine targeting protein dysregulation and to change the Alzheimer's disease treatment paradigm; the treatment potential, designs, proposed mechanisms of action, and potential administration of birtamimab, prasinezumab, PRX004, PRX005, PRX012, and our dual Aβ-tau vaccine; plans for future clinical studies of birtamimab, prasinezumab, PRX004, PRX005, PRX012, and our dual Aβ-tau vaccine; amounts we might receive under our collaborations with Roche, Bristol Myers Squibb, and Novo Nordisk; potential indications and the potential superior attributes and efficacy of novel epitopes and antibodies we have identified in our programs; and our potential to advance, initiate, and complete IND enabling studies for our discovery and preclinical programs. These forward-looking 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 November 4, 2021, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. This overview is made as of January 5, 2022, and we undertake no obligation to update publicly any forward-looking statements contained in this presentation as a result of new information, future events, or changes in our expectations.

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Our Mission is to Make a Real Impact for Patients

We are pioneering protein dysregulation science

to advance novel medicines for diseases caused by misfolded proteins. These devastating conditions include neurodegenerative and rare peripheral amyloid diseases, which affect millions of people and their families worldwide.

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

Neuroscience

Rare Peripheral Amyloid Diseases

Alzheimer's	Parkinson's
disease (AD)	disease (PD)

Amyloid light chain amyloidosis (AL)

Transthyretin amyloidosis (ATTR)

50 million

People worldwide living with Alzheimer's disease or other

dementias1

6th

Leading cause of death in United States5

$1.1 trillion

In annual US healthcare costs by 2050 from AD and other dementias6

10 million

People living with PD worldwide2

Fastest increasing

Neurodegenerative disease6

$52 billion

In overall economic burden in the US7

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

450,000

Estimated number of patients worldwide with wtATTR or hATTR4

2.08 years

Median overall survival New York Heart Association class III patients

with ATTR cardiomyopathy8

1 Patterson C. World Alzheimer Report 2018, 2 Parkinson's Foundation. Understanding Parkinson's. Statistics, 3 Zhang et al, 2019; Kumar et al 2012; VITAL study; Clearview Analysis, 4 Gonzalez-Lopez et al, 2017; Mauer et al, 2016; Gagliardi et al, 2018, 5Alzheimer's Disease Fact Sheet, National Institute on Aging, NIH, 6 Dorsey, E Ray et al 2018; The Emerging Evidence of the Parkinson Pandemic; Journal of Parkinson's disease, 6

Alzheimer's Association Facts and Figures Report 2021, 7 The Economic Burden of Parkinson's Disease - The Michael J. Fox Foundation, 8 Kumar et al 2012, 8. Pinney J et al. 2013; Gonzalez-Lopez E et al. 2017

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Our Team has Pioneered Multiple Scientific Advances in Protein Dysregulation

Our Legacy Includes Foundational Discoveries in the Understanding of Alzheimer's

Disease

1986	1996	2012
Athena	Athena acquired	Prothena spins-out
Neurosciences	by Elan	from Elan with a wholly-owned
founded		drug discovery platform

Pioneered fundamental discoveries elucidating

the roles amyloid, 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-terminus antibody in brains from AD patients2

Discovered biological cause of ARIA and vascular recovery following anti-Aβ immunotherapy3

Developed PRX012, best-in-classanti-Aβ product

candidate, with 10X greater binding potency vs.

aducanumab4

1Games, 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 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.	4 PRX012 Induces Microglia-Mediated Clearance of Pyroglutamate-Modified and -Unmodified Aß in Alzheimer's Disease Brain Tissue presented at	5
AAIC 2021