- Data from PRX012, PRX005 and PRX123 programs showcase promise
of Prothena’s pipeline and commitment to transform the care of
patients with Alzheimer's disease
Prothena 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’s disease, PRX005, PRX012 and PRX123,
at the Alzheimer’s Association International Conference® 2023
(AAIC®) being held July 16-20, 2023 in Amsterdam, Netherlands and
virtually.
“Ending Alzheimer’s disease with cutting-edge science is our
mission. Our posters at AAIC exemplify our multiple efforts to
continue bringing innovation to the Alzheimer’s disease field,”
said Wagner Zago, Ph.D., Chief Scientific Officer, Prothena. “From
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.”
PRX005 Phase 1 Clinical Trial, Single Ascending Dose (SAD)
Portion
Poster 74181: 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
The 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%).
On July 10, 2023, Prothena announced 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.
PRX123 Preclinical Study Results
Poster #82687: Immunological response to dual Aβ/Tau vaccine
PRX123 surrogate and effects on brain amyloid plaques in rapidly
depositing transgenic animal model
Preclinical results demonstrated that a PRX123 vaccine surrogate
elicited robust antibody responses that bound with high avidity to
Aβ plaques in Alzheimer’s disease brain ex vivo and significantly
reduced Aβ brain plaques in a transgenic mouse model of Alzheimer’s
disease pathology. The results support the continued development of
PRX123, a dual Aβ-tau conjugated linear peptide vaccine designed to
treat and/or prevent Alzheimer’s disease, and represent the first
time that a dual target vaccine for Alzheimer’s disease has been
shown to reduce pathology in a transgenic animal model.
PRX012 Preclinical Study Results (encore
presentation)
Poster #74811: Binding Characteristics of Surrogate PRX012
Demonstrate Potent Engagement of Toxic Aβ Protofibrils and Robust
Clearance of Pyroglutamate-Modified Aβ
Results from two preclinical studies were presented comparing a
PRX012-surrogate* (PRX012s) to lecanemab and donanemab†. 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 Aβ protofibrils when compared to
lecanemab, tested under the same conditions. In the second study,
ex vivo using post-mortem Alzheimer’s disease brain tissue, PRX012s
demonstrated to robustly clear pyroglutamate-modified Aβ deposited
in plaques more potently than donanemab.
About PRX005
PRX005 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’s 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’s
disease. Recent publications suggest that during the course of
Alzheimer’s disease progression, tau appears to spread throughout
the brain via synaptically-connected pathways; this propagation of
pathology is thought to be mediated by tau “seeds” 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’s 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’s 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.
About the Global Neuroscience R&D Collaboration
This 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’s 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.
About PRX123
PRX123, a potential first-in-class investigational dual Aβ/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 Aβ and MTBR-tau to simultaneously promote amyloid
clearance and blockade of pathogenic tau.
About PRX012
PRX012, an investigational next-generation anti-Aβ antibody, was
designed as a subcutaneous IgG1 mAb to target aggregated forms of
Aβ, including protofibrils and plaques, with high binding affinity.
PRX012 is currently being investigated in a Phase 1 clinical trial
for the treatment of Alzheimer’s disease. Preclinical data have
demonstrated binding of PRX012 to beta amyloid plaques and
oligomers with high affinity, allowing effective Aβ 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 Aβ plaque
in brain tissue at concentrations of PRX012 estimated to be
clinically achievable in the central nervous system with
subcutaneous delivery.
About Alzheimer’s Disease
Alzheimer’s 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’s disease or other dementias. Alzheimer’s disease is the
most common neurodegenerative disorder. There is an urgent need for
therapies that slow the progression and ultimately prevent
Alzheimer’s disease to address this global healthcare crisis.
Prothena’s Alzheimer’s disease portfolio spans next generation
antibody immunotherapy, small molecule, and vaccine approaches,
geared toward building upon first generation treatments to advance
the treatment paradigm.
About Prothena
Prothena 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’s pipeline includes both
wholly-owned and partnered programs being developed for the
potential treatment of diseases including AL amyloidosis, ATTR
amyloidosis, Alzheimer’s disease, Parkinson’s disease and a number
of other neurodegenerative diseases. For more information, please
visit the Company’s website at www.prothena.com and follow the
Company on Twitter @ProthenaCorp.
Forward-Looking Statements
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
“Risk Factors” 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.
* “Surrogate” is defined as an antibody with >99.5% homology,
the same binding epitope and equivalent binding profile to
different forms of Aβ where directly compared.
† Lecanemab and donanemab were generated from publicly available
sequences
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version on businesswire.com: https://www.businesswire.com/news/home/20230717153986/en/
Media and Investor Contact:
Media Michael Bachner, Senior Director, Corporate Communications
609-664-7308, michael.bachner@prothena.com
Investors Mark Johnson, CFA, Vice President, Investor Relations
650-417-1974, mark.johnson@prothena.com
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