Prothena : Corporate Overview

Prothena Corporate Overview

September 2021

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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 2021 and beyond; our goal of building a protein dysregulation platform; the treatment potential, designs, and proposed mechanisms of action of birtamimab, prasinezumab, PRX004, PRX005, and PRX012; plans for future clinical studies of birtamimab, prasinezumab, PRX004, PRX005, and PRX012; amounts we might receive under our collaborations with Roche, Bristol Myers Squibb and Novo Nordisk; the expected timing of reporting data from prior clinical studies of birtamimab and the Phase 2 clinical study of prasinezumab; 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 August 5, 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 September 8, 2021, 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 Proven Scientific Platform Delivering Transformational Therapeutics

Scientific Platform:

1. Epitope: Target optimal region
2. Specificity and High Affinity: Spare normal biology
3. Mechanism: Engage the right pharmacology

Prothena Today:

• Translation to clinical POC
• Potential Blockbuster indications
• Strong corporate foundation

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Epitope

• Empirical screening
• Superior and consistent efficacy in multiple preclinical models

2

Specificity

• Neoepitope

• Cryptic Epitope

• Avidity

3 Mechanism

• Clearance
• Neutralization
• Disaggregation
• Downregulation
• Antagonism

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Path for Sustainable Growth

Clinical

Protein Dysregulation

Platform

Robust and proven

discovery and development engine

Wholly-owned Phase 3 program

Two Partnered Phase 2 Programs

Five potential IND's from discovery engine

Collaboration

Strong collaborations with Roche, Bristol Myers Squibb and Novo Nordisk1

Significant potential partner payments could further add to pro forma 2Q21 cash of $543 million2

Commercial

Transition to fully-integrated commercial biotech

1In July 2021 Novo Nordisk acquired PRX004 and broader ATTR amyloidosis program and gained full worldwide rights. Prothena is eligible to receive up to $1.23 billion in total consideration.

2Includes $402.5 million of cash, cash equivalents and restricted cash at end of 2Q21, plus $80 million option from Bristol Myers Squibb announced in June (received in 3Q21), and $60 in upfront payment (received) from Novo Nordisk for ATTR program announced in July

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Robust R&D Pipeline

Focused on rare peripheral amyloid and neurodegenerative diseases

Peripheral
Rare	Amyloid

Neurodegenerative

PROGRAM/TARGET	COMMERCIAL	DISCOVERY	PRE-	PHASE 1	PHASE 2	PHASE 3	NEXT MILESTONE
RIGHTS	CLINICAL
Birtamimab / AL		AFFIRM-AL (Phase 3, under SPA1 agreement with FDA)			•	Present VITAL 9mo results at
AL Amyloidosis					upcoming medical meeting
PRX004 / ATTR		Phase 1 (Complete)					•	$40 million near-term clinical
ATTR Amyloidosis							milestone
Prasinezumab / αSyn		PASADENA (Phase 2)					•	Present Part 2 of PASADENA at
Parkinson's Disease		PADOVA (Phase 2b)						upcoming medical meeting
PRX005 / Tau								• Potential $55M option payment
Alzheimer's Disease									for global rights at end of P1
PRX012 / Aβ								• IND 1Q22
Alzheimer's Disease
Undisclosed								•	IND 2022
AD in Down Syndrome
Undisclosed								•	IND	mAb
Neurodegeneration
Vaccine / Aβ + Tau										Small
							•	IND 2023	Molecule
Alzheimer's Disease
TDP-43								•	IND	Vaccine
ALS								Undisclosed

1 Primary endpoint of all-cause mortality at p≤0.10 under the Special Protocol Assessment (SPA) agreement with FDA; Aβ, Abeta; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; mAb, monoclonal antibody

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