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, PRX004 for the potential treatment of ATTR amyloidosis, and a portfolio of programs for the potential treatment of Alzheimer’s disease including PRX012 that targets Aβ (Amyloid beta).

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

Target & Product

Indication

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

Birtamimab

AL

AL
Amyloidosis

Phase 3

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

Prasinezumab

α-SYNUCLEIN

Parkinson’s Disease

Phase 2

7-10 MILLION
patients globally

PRX004

ATTR

ATTR Amyloidosis

Phase 1

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

PRX005

Tau

Alzheimer’s Disease

Preclinical

50 MILLION
patients globally

PRX012

Alzheimer’s Disease

Preclinical

50 MILLION
patients globally

Undisclosed

AD in Down Syndrome

Disc

50% of patients
with Down syndrome
60 years or older

Undisclosed

Neuro-degeneration

Disc

Vaccine

Aβ + Tau

Alzheimer’s Disease

Disc

50 MILLION
patients globally

TDP-43

ALS

Disc

750,000+
patients globally

Modality Undisclosed

Birtamimab

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.

  • 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

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)