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- \nData from oral presentation adds to growing body of evidence supporting the profile of PRX012, which is designed to target all aggregated forms of amyloid beta with high binding potency\n<\/li>\n
- \nDemonstrated 20-fold higher affinity to amyloid beta soluble protofibrils when compared to lecanemab\n<\/li>\n
- \nClears pyroglutamate-modified amyloid beta at lower concentrations when compared to donanemab\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 announced new preclinical data from its PRX012 program, a potential best-in-class anti-amyloid beta (A\u03b2) product candidate in development for the treatment of Alzheimer\u2019s disease, at the 2023 International Conference on Alzheimer\u2019s and Parkinson\u2019s Diseases and related neurological disorders (AD\/PD) in Gothenburg, Sweden.\n<\/p>\n\nTo build a more in-depth understanding of the profile of PRX012 and its potential as a best-in-class anti-A\u03b2 treatment for Alzheimer\u2019s disease, two preclinical studies presented in an oral presentation at AD\/PD 2023 compare a PRX012-surrogate*<\/sup> (PRX012s) to approved and investigational molecules. Surface Plasmon Resonance (SPR) was used to compare PRX012s to lecanemab+<\/sup> and showed that PRX012s had approximately 20-fold higher affinity to A\u03b2 protofibrils as compared to lecanemab when tested under the same conditions. This result was largely driven by a slower binding dissociation rate of PRX012s versus lecanemab.\n<\/p>\n
\nThe second study, an ex vivo study using post-mortem Alzheimer\u2019s disease brain tissue, was designed to test the ability of PRX012s to clear pyroglutamate-modified A\u03b2 deposited in plaques. Study results showed that lower concentrations of PRX012s induced more potent and robust clearance of pyroglutamate-modified A\u03b2 as compared to donanemab+<\/sup>. In the experiment, microglia simultaneously phagocytosed non-pyroglutamate-modified A\u03b2 and pyroglutamate-modified A\u03b2 in the presence of PRX012s, indicating that high opsonization efficiency of plaques by PRX012s was sufficient to clear both forms of A\u03b2.\n<\/p>\n
\n\u201cThese new preclinical data add to the scientific rationale of the PRX012 program, which has the potential to deliver a next-generation Alzheimer\u2019s disease treatment and enable a more convenient administration for patients and caregivers,\u201d said Wagner Zago, Ph.D., Chief Scientific Officer at Prothena. \u201cWith more than 55 million people worldwide estimated to be living with Alzheimer\u2019s disease or other dementias, the timely delivery of improved disease modifying treatments is critical for these patients and their families. Prothena is committed to delivering a patient-centric, best-in-class A\u03b2-targeting antibody with the potential to robustly and safely deplete A\u03b2 plaques.\u201d\n<\/p>\n
\nThese data add to the growing body of evidence supporting the profile of PRX012, which is designed to target all aggregated forms of A\u03b2 with high binding potency. The data further support the ongoing clinical development of PRX012 as a potential best-in-class treatment for Alzheimer\u2019s disease that could enable improved access and more convenient administration for patients and caregivers.\n<\/p>\n
Additional Prothena Activities at AD\/DP 2023<\/b><\/p>\n
\nOther activities at AD\/PD 2023 showcased Prothena\u2019s broad participation at this year’s congress bringing together thought leaders in Alzheimer\u2019s disease research, including Prothena leadership, at a company-sponsored Symposium titled E<\/i>ntering the Era of Disease-Modifying Treatments for AD: Taking Stock of Today and Looking to Tomorrow<\/i>. Two Forum Discussions, Immunotherapies in AD: From Basics to Approval<\/i> and Anti-Tau Therapies in Clinical Trials<\/i> also featured Prothena\u2019s scientific leadership. Prothena\u2019s prasinezumab development partner Roche also contributed poster and oral presentations highlighting aspects of the Phase 2 PASADENA study of prasinezumab for the treatment of Parkinson\u2019s disease.\n<\/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 multiple aggregated forms of A\u03b2, including protofibrils and plaques, with high binding affinity. PRX012 is currently being investigated in Phase 1 clinical studies for the treatment of Alzheimer\u2019s disease. Preclinical data have demonstrated binding of PRX012 to beta amyloid plaques and oligomers with high affinity, resulting in effective A\u03b2 plaque occupancy and removal at relatively lower antibody concentrations, potentially enabling lower volumes of administration 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.\n<\/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. More than 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.\n<\/p>\n
About Prasinezumab<\/b><\/p>\n
\nPrasinezumab is a humanized monoclonal antibody that targets a carboxyl terminal epitope of alpha-synuclein, a protein found in neurons that can aggregate and spread from cell to cell, resulting in the neuronal dysfunction and loss that causes Parkinson\u2019s disease. Prasinezumab is designed to block the cell-to-cell transmission of the aggregated, pathogenic forms of alpha-synuclein in Parkinson’s disease, thereby slowing clinical decline. In December 2013, Prothena and Roche entered into a worldwide collaboration to develop and commercialize antibodies that target alpha-synuclein, including prasinezumab. For more information on the Phase 2b PADOVA clinical study of prasinezumab in patients with early Parkinson’s disease, visit clinicaltrials.gov (NCT#04777331).\n<\/p>\n
About Parkinson’s Disease<\/b><\/p>\n
\nParkinson’s disease is a progressive degenerative disorder of the entire nervous system that affects one in 100 people over age 60. An estimated seven to 10 million people are living with Parkinson’s disease worldwide. It is the second most common neurodegenerative disorder after Alzheimer’s disease. The disease is characterized by the neuronal accumulation of aggregated alpha-synuclein in the central nervous system and peripheral nervous system that results in a wide spectrum of worsening progressive motor and non-motor symptoms. While diagnosis relies on motor symptoms classically associated with Parkinson’s disease, non-motor symptoms may present many years earlier. Current treatments for Parkinson’s disease are symptomatic and only address a subset of symptoms such as motor impairment, dementia, or psychosis. There are currently no treatments available that target the underlying cause of the disease and can slow its progression.\n<\/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.\n<\/p>\n
Forward-looking Statements<\/b><\/p>\n
\nThis 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 PRX012 and prasinezumab. 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 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 28, 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.\n<\/p>\n
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*<\/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.\n<\/p>\n
+<\/sup> Lecanemab and donanemab were generated from publicly available sequences.\n<\/p>\n
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\nMedia
\n
Michael Bachner, Senior Director, Corporate Communications
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609-664-7308, michael.bachner@prothena.com<\/a><\/p>\n
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