CORPORATE OVERVIEW
May 2024
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 2024, 2025, 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 PRX012, BMS-986446/PRX005, PRX123, birtamimab, NNC6019/PRX004, and prasinezumab; potential indications (including prevalence) and attributes of epitopes and antibodies we have identified in our programs; plans for ongoing and future clinical trials of PRX012, BMS-986446/PRX005, PRX123, birtamimab, NNC6019/PRX004, and prasinezumab; the expected timing of reporting data from clinical trials of birtamimab, PRX012, prasinezumab, and NNC6019, including any updates regarding our ongoing Phase 1 clinical trial evaluating PRX012 in 2024 and any topline study results for our Phase 3 AFFIRM-AL clinical trial between 4Q 2024 and 2Q 2025; 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 May 8, 2024, and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. This overview is made as of May 8, 2024, 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.
2
Our Mission Today
We are Focused on Delivering Life-Saving Therapies…
…for unmet medical needs caused by
diseases of protein dysregulation
3
We are Addressing Devastating Proteinopathies Affecting Millions of Patients and Families Worldwide
NEURODEGENERATIVE DISEASES | 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 States6
$1 trillion
In annual US healthcare costs by 2050 from AD and other dementias8
Parkinson's
disease (PD)
10 million
People living with PD worldwide2
Fastest increasing
Neurodegenerative disease7
$52 billion
In overall economic burden in the US9
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 amyloidosis4
Transthyretin amyloidosis (ATTR)
450,000
Estimated number of patients worldwide with wtATTR or ATTRv5
2.08 years
Median overall survival New York Heart Association class
- patients with ATTR cardiomyopathy10
wtATTR: Wild-Type ATTR. ATTRv: Hereditary amyloid transthyretin. | ||
1 | Alzheimer's Disease International. Dementia Statistics, 2 Parkinson's Foundation. Understanding Parkinson's. Statistics, 3 Kumar N, et al. 2022 Orphanet J Rare Dis; Quock T, et al. 2018 Blood Advances, 4 Levin M, et al. Available at: | |
https://www.myamyloidosisteam.com/resources/stages-of-amyloidosis; Kumar S, et al. 2012 J Clin Oncol., 5 Gonzalez-Lopez et al, 2017; Mauer et al, 2016; Gagliardi et al, 2018, 6 2021 Alzheimer's Disease Fact Sheet, National Institute on Aging, NIH, | ||
4 | 7 | 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, |
8 | Alzheimer's Association Facts and Figures Report 2022, 9 The Economic Burden of Parkinson's Disease - The Michael J. Fox Foundation, 10 Kumar et al 2012, Pinney J et al. 2013; Gonzalez-Lopez E et al. 2017. |
Our Biology-Directed Engine Propels Prothena's
Progress Across our Broad Pipeline
Therapeutics engineered to
optimally eliminate pathogenic
proteins while preserving
normal biology
Disease- | |||
Driven | |||
Antibody | |||
Engineering | |||
Deep | |||
expertise in | Expert | BIOLOGY- | Greater |
determining | |||
optimal | Epitope | DIRECTED | Patient |
epitopes to | Mapping | ENGINE | Impact |
be targeted |
for maximal
efficacy
Pathophysiology
Directed
Targeting
Product
candidates with best- in-class potential to slow, stop, prevent protein- opathies
Multiple Clinical Programs Ongoing
Wholly-owned Phase 3 program
Three partnered Phase 2 programs
Wholly-owned Phase 1 program
Two new INDs cleared by FDA
Strong Collaborations Established
Collaborations with Bristol Myers Squibb,
Novo Nordisk1 and Roche
Leveraging our Phase 3 Rare Peripheral Amyloid Disease Program to Support Commercial Buildout
Transition into a fully-integrated commercial biotech through our lead rare disease program
Targets proteins with the greatest effect on disease, not limited by a single platform or technology
5 | 1 | In July 2021 Novo Nordisk acquired NNC6019 (formerly PRX004) and broader ATTR amyloidosis program |
and gained full worldwide rights. Prothena is eligible to receive up to $1.23 billion in total consideration. | ||
Robust R&D Pipeline
FOCUSED ON NEURODEGENERATIVE AND RARE PERIPHERAL AMYLOID DISEASES
PROGRAM/ | PROTEIN TARGET | DISCOVERY | PRE-CLINICAL | PHASE 1 | PHASE 2 | PHASE 3 | GLOBAL | ||||||
INDICATION | PARTNER4,5 | ||||||||||||
Birtamimab | SPA1 ODD2 | Fast 3 | Kappa & Lambda | AFFIRM-AL (Phase 3) | |||||||||
AL amyloidosis | Light Chain | ||||||||||||
Track | |||||||||||||
Prasinezumab | α | ||||||||||||
-Synuclein | PASADENA (Phase 2) | PADOVA (Phase 2b) | ||||||||||||
Parkinson's disease | (C-terminus) | ||||||||||||
NNC6019 (PRX004) | Transthyretin | Phase 2 | |||||||||||
ATTR amyloidosis | (misTTR) | ||||||||||||
BMS-986446 (PRX005) | Tau | Phase 2 | |||||||||||
Alzheimer's disease | (MTBR) | ||||||||||||
PRX012 | Fast | Aβ | ASCENT (Phase 1) | ||||||||||
Alzheimer's disease | (N-terminus) | ||||||||||||
Track3 | |||||||||||||
PRX123 | Fast 3 | Aβ + Tau | IND cleared | ||||||||||
Alzheimer's disease | |||||||||||||
Track | |||||||||||||
PRX019 | Undisclosed Target | IND cleared | |||||||||||
Neurodegeneration | |||||||||||||
TDP-43 | TDP-43 | ||||||||||||
ALS | |||||||||||||
Undisclosed | Undisclosed Target | ||||||||||||
AD in Down syndrome | |||||||||||||
Modalities: | mAb | Small Molecule | Vaccine | Undisclosed | |||||||||
6 | Aβ, Abeta; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; mAb, monoclonal antibody. | ||||||||||||
1 Primary endpoint of all-cause mortality at p≤0.10 under the Special Protocol Assessment (SPA) agreement with FDA; 2 Orphan Drug Designation granted by FDA & EMA; 3 FDA Fast Track designation; 4 In July 2021 Novo Nordisk acquired NNC6019 | |||||||||||||
(formerly PRX004) and broader ATTR amyloidosis program and gained full worldwide rights. Prothena is eligible to receive up to $1.23 billion in total consideration; 5 BMS-986446, PRX019 and TDP-43 are part of a Global Neuroscience Research and |
Development Collaboration with Bristol Myers Squibb. BMS has currently opted-in to the global rights for BMS-986446.
Alzheimer's Disease
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, | |
8 | 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
Our Legacy Drives Our Vision to Transform
the Care of Alzheimer's Disease
With unparalleled protein | …We're uniquely positioned to address Alzheimer's | ||
dysregulation expertise… | Disease with a best-in-class portfolio | ||
PRX012, anti-Aβ candidate with potential | |
best-in-class, highly potent binding; | |
designed for improved patient access via | Phase 1 |
subcutaneous delivery5
BMS-986446(PRX005), anti-tau candidate, with potential to reduce pathogenic tau spread6
PRX123, dual Aβ/tau vaccine candidate
designed for treatment and prevention
Phase 2
OUR LEGACY 1-4
IND cleared
9 | 1 Games D, et al.1995 Nature; 2 Zago W, et al. 2013 Alzheimers Dement; 3 Schenk D, et al. 1999 Nature; 4 Rinne, et al. 2010 Lancet Neurol; 5 Skov M, et al. Preclinical data available at: https://tinyurl.com/3zzpmbxh; 6 Dolan P. Preclinical data |
available at: https://tinyurl.com/3kf7pvnd. |
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Prothena Corporation plc published this content on 08 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 08 May 2024 21:06:26 UTC.