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- \nData from PRX012, PRX005 and PRX123 programs showcase promise of Prothena\u2019s pipeline and commitment to transform the care of patients with Alzheimer’s disease<\/p>\n<\/li>\n<\/ul>\n
DUBLIN–(BUSINESS WIRE<\/a>)–
\nProthena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today shared data on three investigational product programs for the treatment and prevention of Alzheimer\u2019s disease, PRX005, PRX012 and PRX123, at the Alzheimer\u2019s Association International Conference\u00ae<\/sup> 2023 (AAIC\u00ae<\/sup>) being held July 16-20, 2023 in Amsterdam, Netherlands and virtually.<\/p>\n\n\u201cEnding Alzheimer\u2019s disease with cutting-edge science is our mission. Our posters at AAIC exemplify our multiple efforts to continue bringing innovation to the Alzheimer\u2019s disease field,\u201d said Wagner Zago, Ph.D., Chief Scientific Officer, Prothena. \u201cFrom two next-generation antibodies with best-in-class potential, PRX012 and PRX005, to our vaccine, PRX123, our goal is to deliver better outcomes for the millions of patients with this devastating disease and ultimately eradicate it altogether.\u201d<\/p>\n
PRX005 Phase 1 Clinical Trial, Single Ascending Dose (SAD) Portion<\/b><\/p>\n
Poster 74181<\/i>: PRX005, A Novel Anti-MTBR Tau Humanized Monoclonal Antibody: Results from the Single Ascending Dose Portion of a First-in-Human Double-Blind, Placebo-Controlled, Phase 1 Clinical Trial<\/i><\/p>\n
\nThe results of the Phase 1 clinical trial SAD portion showed that all three dose level cohorts (low, medium, high) of PRX005 were considered generally safe and well tolerated, meeting the Phase 1 clinical trial SAD portion primary objective and supporting evaluation of doses in the MAD portion of the ongoing Phase 1 clinical trial. PRX005 also met key pharmacokinetic (PK) and immunogenicity secondary endpoints. Plasma drug concentrations of PRX005 increased in a dose-proportional manner. As planned, cerebral spinal fluid (CSF) drug levels were measured in the high dose cohort and reached sufficient CSF concentrations to predict pharmacological targeting of MTBR tau in the central nervous system (CNS) (day 29 CSF:plasma ratio=0.2%).<\/p>\n
\nOn July 10, 2023, Prothena announced<\/a> that Bristol Myers Squibb exercised its $55 million option under the global neuroscience research and development collaboration to obtain the exclusive worldwide commercial rights for PRX005. Bristol Myers Squibb will be responsible for the development, manufacturing, and commercialization of PRX005. All program updates, including results from ongoing and any future PRX005 clinical studies, will be reported by Bristol Myers Squibb going forward.<\/p>\n
PRX123 Preclinical Study Results<\/b><\/p>\n
Poster #82687<\/i>: Immunological response to dual A\u03b2\/Tau vaccine PRX123 surrogate and effects on brain amyloid plaques in rapidly depositing transgenic animal model<\/i><\/p>\n
\nPreclinical results demonstrated that a PRX123 vaccine surrogate elicited robust antibody responses that bound with high avidity to A\u03b2 plaques in Alzheimer\u2019s disease brain ex vivo and significantly reduced A\u03b2 brain plaques in a transgenic mouse model of Alzheimer\u2019s disease pathology. The results support the continued development of PRX123, a dual A\u03b2-tau conjugated linear peptide vaccine designed to treat and\/or prevent Alzheimer\u2019s disease, and represent the first time that a dual target vaccine for Alzheimer\u2019s disease has been shown to reduce pathology in a transgenic animal model.<\/p>\n
PRX012 Preclinical Study Results (encore presentation)<\/b><\/p>\n
Poster #74811<\/i>: Binding Characteristics of Surrogate PRX012 Demonstrate Potent Engagement of Toxic A\u03b2 Protofibrils and Robust Clearance of Pyroglutamate-Modified A\u03b2<\/i><\/p>\n
\nResults from two preclinical studies were presented comparing a PRX012-surrogate*<\/sup> (PRX012s) to lecanemab and donanemab\u2020<\/sup>. In the first study, Surface Plasmon Resonance (SPR) was used to compare PRX012s to lecanemab and showed that PRX012s had approximately 20-fold higher affinity to A\u03b2 protofibrils when compared to lecanemab, tested under the same conditions. In the second study, ex vivo using post-mortem Alzheimer\u2019s disease brain tissue, PRX012s demonstrated to robustly clear pyroglutamate-modified A\u03b2 deposited in plaques more potently than donanemab.<\/p>\n
About PRX005<\/b><\/p>\n
\nPRX005 is designed to be a best-in-class anti-tau antibody that specifically binds with high affinity to the R1, R2, and R3 repeats within the MTBR of tau and targets both 3R and 4R tau isoforms. MTBR tau has been shown in preclinical studies to be involved in the pathological spread of tau. Neurofibrillary tangles composed of misfolded tau proteins, along with amyloid beta plaques, are pathological hallmarks of Alzheimer\u2019s disease. Cell-to-cell transmission of pathogenic extracellular tau and the accumulation of pathogenic tau also correlate with the progression of symptomatology and clinical decline in patients with Alzheimer\u2019s disease. Recent publications suggest that during the course of Alzheimer\u2019s disease progression, tau appears to spread throughout the brain via synaptically-connected pathways; this propagation of pathology is thought to be mediated by tau \u201cseeds\u201d containing the MTBR of tau. Additionally, it has been recently reported that the presence of MTBR fragments in cerebrospinal fluid correlate with dementia stages and tau tangles in Alzheimer\u2019s disease to a higher degree than fragments of other tau regions. In preclinical research, antibodies targeting this region of tau were superior in blocking tau uptake and neurotoxicity, which has been associated with efficacy in Alzheimer\u2019s disease animal models. In these preclinical models, PRX005 demonstrated significant reduction of intraneuronal tau pathology and protection against behavioral deficit in a tau transgenic mouse model and complete blockade of neuronal tau internalization in vitro.<\/p>\n
About the Global Neuroscience R&D Collaboration<\/b><\/p>\n
\nThis global neuroscience research and development collaboration is focused on three proteins implicated in the pathogenesis of several neurodegenerative diseases, including tau, TDP-43 and an undisclosed target. PRX005 is designed to be a best-in-class anti-tau, MTBR-specific antibody for the potential treatment of Alzheimer\u2019s disease and is the first program to advance to the clinic from this collaboration. Prothena is eligible to receive up to an additional $160 million for U.S. rights, up to $110 million for global rights, and up to $1.7 billion for regulatory and commercial milestone payments for a total of up to $2.2 billion, which also includes amounts received to date.<\/p>\n
About PRX123<\/b><\/p>\n
\nPRX123, a potential first-in-class investigational dual A\u03b2\/tau vaccine designed for the treatment and prevention of Alzheimer’s disease, is a dual-target vaccine targeting key epitopes within the N-terminus of A\u03b2 and MTBR-tau to simultaneously promote amyloid clearance and blockade of pathogenic tau.<\/p>\n
About PRX012<\/b><\/p>\n
\nPRX012, an investigational next-generation anti-A\u03b2 antibody, was designed as a subcutaneous IgG1 mAb to target aggregated forms of A\u03b2, including protofibrils and plaques, with high binding affinity. PRX012 is currently being investigated in a Phase 1 clinical trial for the treatment of Alzheimer\u2019s disease. Preclinical data have demonstrated binding of PRX012 to beta amyloid plaques and oligomers with high affinity, allowing effective A\u03b2 plaque occupancy and removal at relatively lower dose ranges, optimal for subcutaneous delivery. Preclinical data have also demonstrated clearance of both pyroglutamate modified and unmodified A\u03b2 plaque in brain tissue at concentrations of PRX012 estimated to be clinically achievable in the central nervous system with subcutaneous delivery.<\/p>\n
About Alzheimer\u2019s Disease<\/b><\/p>\n
\nAlzheimer\u2019s disease is a fatal disease and the most common form of dementia causing increasingly serious symptoms, including confusion, disorientation, mood and behavioral changes, and difficulty speaking, swallowing, and walking. Approximately 55 million people worldwide are estimated to be living with Alzheimer\u2019s disease or other dementias. Alzheimer\u2019s disease is the most common neurodegenerative disorder. There is an urgent need for therapies that slow the progression and ultimately prevent Alzheimer\u2019s disease to address this global healthcare crisis. Prothena\u2019s Alzheimer\u2019s disease portfolio spans next generation antibody immunotherapy, small molecule, and vaccine approaches, geared toward building upon first generation treatments to advance the treatment paradigm.<\/p>\n
About Prothena<\/b><\/p>\n
\nProthena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothena\u2019s pipeline includes both wholly-owned and partnered programs being developed for the potential treatment of diseases including AL amyloidosis, ATTR amyloidosis, Alzheimer\u2019s disease, Parkinson\u2019s disease and a number of other neurodegenerative diseases. For more information, please visit the Company\u2019s website at www.prothena.com<\/a> and follow the Company on Twitter @ProthenaCorp.<\/p>\n
Forward-Looking Statements<\/b><\/p>\n
This press release contains forward-looking statements. These statements relate to, among other things, the treatment potential, designs, proposed mechanisms of action, and potential administration of PRX005, PRX012, and PRX123; and amounts we might receive under our collaboration with BMS. 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 \u201cRisk Factors\u201d sections of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 4, 2023, and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. 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.<\/i><\/p>\n
*<\/sup> \u201cSurrogate\u201d is defined as an antibody with >99.5% homology, the same binding epitope and equivalent binding profile to different forms of A\u03b2 where directly compared.<\/p>\n
\u2020<\/sup> Lecanemab and donanemab were generated from publicly available sequences<\/p>\n
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Media and Investor Contact: <\/b><\/p>\n
\nMedia
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Michael Bachner, Senior Director, Corporate Communications
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609-664-7308, michael.bachner@prothena.com<\/a><\/p>\n\nInvestors
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Mark Johnson, CFA, Vice President, Investor Relations
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650-417-1974, mark.johnson@prothena.com<\/a><\/p>\nKEYWORDS:<\/b> Europe Ireland United Kingdom Netherlands<\/p>\n
INDUSTRY KEYWORDS:<\/b> Science Neurology Biotechnology Research Pharmaceutical Health Mental Health Clinical Trials<\/p>\n
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