Pipeline

Innovating for Patients

Fueled by a deep scientific expertise built over decades of research, Prothena is integrating scientific insights around protein dysregulation to advance a pipeline of therapeutic candidates for a number of rare peripheral amyloid and neurodegenerative diseases.

Prothena’s wholly owned programs include birtamimab for the potential treatment of AL amyloidosis and a portfolio of programs for the potential treatment of Alzheimer’s disease including PRX012 that targets Aβ (amyloid beta) and the company’s dual Aβ-tau vaccine.

Prothena’s collaborations include prasinezumab, which targets alpha-synuclein, with Roche for the potential treatment of Parkinson’s disease, PRX004 for the potential treatment of ATTR amyloidosis with Novo Nordisk, and programs that target tau (PRX005), TDP-43 and an undisclosed target with Bristol-Myers Squibb for the potential treatment of neurodegenerative diseases.

Target & Product

Indication

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

Birtamimab

AL
Amyloidosis

Phase 3

60,000 – 120,000
Mayo Stage IV
patients globally

Learn More

Modality

Prasinezumab

α-SYNUCLEIN

Parkinson’s Disease

Phase 2

7-10 MILLION
patients globally

Learn More

Modality

Commercial Rights

PRX004

ATTR

ATTR Amyloidosis

Phase 1

130k – 490k
NYHA Class III and IV Patients Globally

Learn More

Modality

Commercial Rights

PRX005

Tau

Alzheimer’s Disease

Preclinical

50 MILLION
patients globally

Learn More

Modality

Commercial Rights

PRX012

Aβ

Alzheimer’s Disease

Preclinical

50 MILLION
patients globally

Learn More

Modality

Undisclosed

AD in Down Syndrome

Disc

50% of patients
with Down syndrome
60 years or older

Learn More

Modality

Undisclosed

Neuro-degeneration

Disc

Learn More

Modality

Commercial Rights

Vaccine

Aβ + Tau

Alzheimer’s Disease

Disc

50 MILLION
patients globally

Learn More

Modality

TDP-43

ALS

Disc

750,000+
patients globally

Learn More

Modality Undisclosed

Commercial Rights

Birtamimab PRASINEZUMAB PRX004 Other

Birtamimab

Organ response in patients with AL amyloidosis treated with NEOD001, an amyloid-directed monoclonal antibody
Organ response in patients with AL amyloidosis treated with NEOD001, an amyloid-directed monoclonal antibody
Morie A. Gertz, Heather J. Landau and Brendan M. Weiss;
American Journal of Hematology; DOI: 10.1002/ajh.24563; Published online 21 October, 2016
2A4 Binds Soluble and Insoluble Light Chain Aggregates from AL Amyloidosis Patients and Promotes Clearance of Amyloid Deposits by Phagocytosis
2A4 Binds Soluble and Insoluble Light Chain Aggregates from AL Amyloidosis Patients and Promotes Clearance of Amyloid Deposits by Phagocytosis
Mark Renz, Ronald Torres, Philip J. Dolan, Stephen J. Tam, Jose R. Tapia, Lauri Li, Joshua R. Salmans, Robin M. Barbour, Paul J. Shughrue, Tarlochan Nijjar, Dale Schenk, Gene G. Kinney & Wagner Zago
Amyloid DOI: 10.1080/13506129.2016.1205974 (2016)
First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction
First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction
Morie A. Gertz, Heather Landau, Raymond L. Comenzo, David Seldin, Brendan Weiss, Jeffrey Zonder, Giampaolo Merlini, Stefan Schönland, Jackie Walling, G.G. Kinney, Martin Koller, Dale B. Schenk, Spencer D. Guthrie, Michaela Liedtke
Journal of Clinical Oncology, published online on February 8, 2016; DOI:10.1200/JCO.2015.63.6530
AL Amyloid Imaging and Therapy with a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils
AL Amyloid Imaging and Therapy with a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils
J.S. Wall, S.J. Kennel, A. Williams, T. Richey, A. Stuckey, Y. Huang, S. Macy, R. Donnell, R. Barbour, P. Seubert, D. Schenk
PLoS ONE 7(12):e52686 (2012)
Generation and Characterization of anti-AA Amyloid-Specific Monoclonal Antibodies.
Generation and Characterization of anti-AA Amyloid-Specific Monoclonal Antibodies.
J.S. Wall, S.J. Kennel, T. Richey, A. Allen, A. Stuckey, D.T. Weiss, R. Barbour, P. Seubert, A. Solomon, D. Schenk
Frontiers of Immunology DOI:10.3389/fimmu.2011.00032 (2011)

PRASINEZUMAB

Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease A Randomized Clinical Trial
Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease A Randomized Clinical Trial
Joseph Jankovic, MD; Ira Goodman, MD; Beth Safirstein, MD; Tonya K. Marmon, DrPH; Dale B. Schenk, PhD; Martin Koller,MD, MPH;Wagner Zago, PhD; Daniel K. Ness, DVM, PhD; Sue G. Griffith, MD, PhD, MRCP; Michael Grundman, MD, MPH; Jay Soto, BS; Susanne Ostrowitzki, MD, PhD; Frank G. Boess, PhD; Meret Martin-Facklam, PhD; Joseph F. Quinn, MD; Stuart H. Isaacson, MD; Omid Omidvar, MD; Aaron Ellenbogen, DO; Gene G. Kinney, PhD
JAMA Neurology; DOI: 10.1001/jamaneurol.2018.1487, Published online June 18, 2018.
First-in-human assessment of PRX002, an anti–α-synuclein monoclonal antibody, in healthy volunteers
First-in-human assessment of PRX002, an anti–α-synuclein monoclonal antibody, in healthy volunteers
Dale B. Schenk, Martin Koller, Daniel K. Ness, Sue G. Griffith, Michael Grundman, Wagner Zago, Jay Soto, George Atiee, Susanne Ostrowitzki, and Gene G. Kinney
Movement Disorders, DOI: 10.1002/mds.26878 (2016)
Reducing C-Terminal-Truncated Alpha-Synuclein by Immunotherapy Attenuates Neurodegeneration and Propagation in Parkinson’s Disease-Like Models
Reducing C-Terminal-Truncated Alpha-Synuclein by Immunotherapy Attenuates Neurodegeneration and Propagation in Parkinson’s Disease-Like Models
D. Games, E. Valera, B. Spencer, E. Rockenstein, M. Mante, A. Adame, C. Patrick, K. Ubhi, S. Nuber, P. Sacayon, W. Zago, P. Seubert, R. Barbour, D. Schenk, and E. Masliah
The Journal of Neuroscience, July 9, 2014 · 34(28):9441-9454 · 9441
Axonopathy in an a-Synuclein Transgenic Model of Lewy Body Disease Is Associated with Extensive Accumulation of C-Terminal-Truncated a-Synuclein
Axonopathy in an a-Synuclein Transgenic Model of Lewy Body Disease Is Associated with Extensive Accumulation of C-Terminal-Truncated a-Synuclein
D. Games, P. Seubert, E. Rockenstein, C. Patrick, M.Trejo, K. Ubhi, B. Ettle, M. Ghassemiam, R. Barbour, D. Schenk, S. Nuber, E. Masliah
The American Journal of Pathology, Vol. 182, No. 3, March 2013
Axonopathy in an a-Synuclein Transgenic Model of Lewy Body Disease Is Associated with Extensive Accumulation of C-Terminal-Truncated a-Synuclein
Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
E. Masliah, E. Rockenstein, M. Mante, L. Crews, B. Spencer, A. Adame, C. Patrick, M. Trejo, K. Ubhi, T. Rohn, S. Mueller-Steiner, P. Seubert, R. Barbour, L. McConlogue, M. Buttini, D. Games, D. Schenk
PLoS ONE 6 (4), 1-17 (2011)

PRX004

Novel Conformation-specific Monoclonal Antibodies Against Amyloidogenic Forms of Transthyretin
Novel Conformation-specific Monoclonal Antibodies Against Amyloidogenic Forms of Transthyretin

Jeffrey N. Higaki, Avi Chakrabartty, Natalie J. Galant, Kevin C. Hadley, Bradley Hammerson, Tarlochan Nijjar, Ronald Torres, Jose R. Tapia, Joshua Salmans, Robin Barbour, Stephen J. Tam, Ken Flanagan, Wagner Zago & G. G. Kinney
Amyloid, DOI:10.3109/13506129.2016.1148025 (2016)

OTHER

Vascular alterations in PDAPP mice following anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities (ARIA)
Vascular alterations in PDAPP mice following anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities (ARIA)
W. Zago, S. Schroeter, T. Guido, K. Khan, P. Seubert, T. Yednock, D. Schenk, K.M. Gregg, D. Games, F. Bard, G.G. Kinney
Alzheimers Dementia 9, S105–S115 (2013)
Neutralization of soluble synaptotoxic Aß species by antibodies is epitope specific
Neutralization of soluble synaptotoxic Aß species by antibodies is epitope specific
W. Zago, M. Buttini, T.A. Comery, C. Nishioka, P. Seubert, D. Games, F. Bard, D. Schenk, G.G. Kinney
Journal of Neuroscience, 32:2696-2702 (2012)
Sustained levels of antibodies against Aß in amyloid-rich regions of the CNS following intravenous dosing in human APP transgenic mice
Sustained levels of antibodies against Aß in amyloid-rich regions of the CNS following intravenous dosing in human APP transgenic mice
F. Bard, M. Fox, S. Friedrich, P. Seubert, D. Schenk, G.G. Kinney, T. Yednock
Exp Neurol., 238:38-43 (2012)
Structural Correlates of Antibodies Associated with Acute Reversal of Amyloid β-related Behavioral Deficits in a Mouse Model of Alzheimer Disease
Structural Correlates of Antibodies Associated with Acute Reversal of Amyloid β-related Behavioral Deficits in a Mouse Model of Alzheimer Disease
G. Basi, H. Feinberg, F. Oshidari, J. Anderson, R. Barbour, J. Baker, T.A. Comery, L. Diep, D. Gill, K. Johnson-Wood, A. Goel, K. Grantcharova, M. Lee, J. Li, A. Partridge, I. Griswold-Prenner, N. Piot, D. Walker, A. Widom, M.N. Pangalos, P. Seubert, J.S. Jacobsen, D. Schenk, W.I. Weis
Journal of Biological Chemistry 285(5):3417-3427 (2010)
Effects of α-Synuclein Immunization in a Mouse Model of Parkinson’s Disease
Effects of α-Synuclein Immunization in a Mouse Model of Parkinson’s Disease
E. Masliah, E. Rockenstein, A. Adame, M. Alford, L. Crews, M. Hashimoto, P. Seubert, M. Lee, J. Goldstein, T. Chilcote, D. Games, D. Schenk
Neuron 46, 857-868 (2005)
Aβ42 Immunization in Alzheimer’s Disease Generates Aβ N-Terminal Antibodies
Aβ42 Immunization in Alzheimer’s Disease Generates Aβ N-Terminal Antibodies
M. Lee, F. Bard, K. Johnson-Wood, C. Lee, K. Hu, S. Griffith, R. Black, D. Schenk, P. Seubert
Ann. Neurol. 58, 430-435 (2005)
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
D. Schenk, R. Barbour, W. Dunn, G. Gordon, H. Grajeda, T. Guido, K. Hu, J. Huang, K. Johnson-Wood, K. Khan, D. Kholodenko, M. Lee, Z. Liao, I. Lieberburg, R. Motter, L. Mutter, F. Soriano, G. Shopp, N. Vazquez, C. Vendevert, S. Walker, M. Wogulis, T. Yednock, D. Games, P. Seubert
Nature, 400, 173-177 (1999)

Pipeline

Target & Product

Indication

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

Birtamimab

AL Amyloidosis

Prasinezumab

Parkinson’s Disease

PRX004

ATTR Amyloidosis

PRX005

Alzheimer’s Disease

PRX012

Alzheimer’s Disease

Undisclosed

AD in Down Syndrome

Undisclosed

Neuro-degeneration

Vaccine

Alzheimer’s Disease

TDP-43

ALS

Modality Undisclosed

Birtamimab

PRASINEZUMAB

PRX004

OTHER

AL
Amyloidosis