Full Press Release Details
Prothena Provides Update on PRX012 and Announces Results from the Phase 1 ASCENT Clinical Program
DUBLIN, Ireland, August 27 - Prothena Corporation plc (NASDAQ:PRTA), today announced results from the Phase 1 ASCENT clinical program in
participants with early symptomatic Alzheimer's disease (AD). As previously communicated, Prothena plans to explore potential partnership interest to advance PRX012 and its preclinical PRX012-TfR
(transferrin receptor) antibody.
The Phase 1 ASCENT clinical program results demonstrated PRX012 as a potential once-monthly, subcutaneous anti-amyloid
beta (A ) antibody with stable pharmacokinetics, low anti-drug antibodies, low injection site reactions, and dose- and time-dependent reductions in amyloid plaque. At the 400 mg dose level, PRX012
demonstrated a mean reduction in amyloid PET to 27.47 centiloids (CL) at month 12; FDA approved anti-A antibodies have defined amyloid negativity thresholds
of 30 CL or 24.1 CL. However, PRX012 was associated with higher overall ARIA-E rates relative to FDA approved
anti-A antibodies, making PRX012 less appropriate for the patients studied in the ASCENT clinical program. When ARIA-E did
occur, the characteristics were similar to those reported following treatment with other anti-A antibodies.
Based on the profile observed in the ASCENT clinical program and feasibility work already completed on its
preclinical A -transferrin receptor antibody surrogate, Prothena believes this approach may represent an opportunity to significantly lower the risk of ARIA and quickly reduce amyloid plaque with a
once-monthly subcutaneous administration. Initial preclinical studies have demonstrated substantially increased brain exposure and facilitated rapid targeting of A plaques in an APP/PS1 transgenic mouse
"On behalf of our entire team, we extend our continued appreciation to the patients, families, investigators, and staff whose dedication and
collaboration enabled the Phase 1 ASCENT clinical program to achieve its objectives," said Chad Swanson, Ph.D., Chief Development Officer, Prothena. "We plan to explore potential partnership interest to further develop PRX012 and PRX012-TfR."
Prothena does not plan to publicly share additional data from the ASCENT clinical program while it
expects to explore potential partnership interest to advance PRX012 and PRX012-TfR.
Phase 1 ASCENT Clinical
The Phase 1 ASCENT clinical program includes ASCENT-1: a randomized, double-blind, placebo-controlled
single-ascending-dose trial; ASCENT-2: a randomized, double-blind, placebo-controlled six-month multiple-dose trial; and
ASCENT-3: a twelve-month open-label extension trial. The objectives of the ASCENT clinical program were to determine the safety, tolerability, immunogenicity, and pharmacokinetics of PRX012. The ASCENT-2 and ASCENT-3 trials also evaluated the pharmacodynamics of PRX012, including amyloid plaque deposition as measured by positron emission tomography (PET), in
participants with early symptomatic AD.
The results include data from the five ASCENT-2 Group A cohorts in 228
participants with early symptomatic AD who are either APO 4 non-carriers or heterozygous carriers ranging in doses of PRX012 from 45 mg to 400 mg, randomized to
PRX012 or placebo in a 3:1 ratio. Additional amyloid plaque reduction data from an interim read-out of ASCENT-3, the open-label extension (OLE) trial, was included.
ASCENT-2 Group A: Adverse Events1
| Placebo (n=57) | 45 mg (n=25) | 70 mg (n=24) | 200 mg 2 (n=97) | 400 mg (n=24) | ||||||||||||||||
| Treatment Emergent Adverse Events (TEAE) | 33 (57.9%) | 10 (40.0%) | 13 (54.2%) | 66 (68.0%) | 18 (75.0%) | |||||||||||||||
| Treatment Emergent Serious Adverse Event (TESAE) | 5 (8.8%) | 2 (8.0%) | 1 (4.2%) | 7 (7.2%) | 1 (4.2%) | |||||||||||||||
| Study drug related TESAE | 0 | 0 | 1 (4.2%) | 5 (5.2%) | 1 (4.2%) | |||||||||||||||
| TEAE Leading to Withdrawal of Study Drug | 0 | 0 | 1 (4.2%) | 4 (4.1%) | 0 |
| TEAE Leading to Withdrawal from the Study | 0 | 0 | 1 (4.2%) | 1 (1.0%) | 0 | |||||||||||||||
| Death | 0 | 1 (4.0%) | 0 | 0 | 0 | |||||||||||||||
| Death due to Study Drug | 0 | 0 | 0 | 0 | 0 | |||||||||||||||
| Overall ARIA | 4 (7.0%) | 4 (16.0%) | 5 (20.8%) | 41 (42.3%) | 10 (41.7%) | |||||||||||||||
| ARIA-E | 1 (1.8%) 3 | 3 (12.0%) | 2 (8.3%) | 37 (38.1%) | 10 (41.7%) | |||||||||||||||
| ARIA-H | 4 (7.0%) | 3 (12.0%) | 4 (16.7%) | 29 (29.9%) | 8 (33.3%) | |||||||||||||||
| Concurrent ARIA-E and ARIA-H | 0 | 2 (8.0%) | 1 (4.2%) | 24 (24.7%) | 8 (33.3%) |
PRX012 was generally well-tolerated across all dose cohorts of the trial. Injection site reactions in participants
treated with PRX012 were low (4.1%). Treatment emergent anti-drug antibodies were low and generally transient with titer values close to the assay's detection threshold. There was one death in the study in the 45 mg dose cohort, which was
determined by the investigator to be not related to study drug.
Group A: Amyloid PET Centiloid (CL) Values
ASCENT-2 and ASCENT-3 Interim Data
| Placebo | 45 mg | 70 mg | 200 mg 1 | 400 mg | ||||||||||||||||
| Baseline Mean CL | 77.74 (n=49 | ) | 75.64 (n=22 | ) | 75.62 (n=19 | ) | 75.47 (n=86 | ) | 70.95 (n=23 | ) | ||||||||||
| 6 Months Mean CL (double-blind placebo controlled) | 77.84 (n=49 | ) | 77.39 (n=22 | ) | 67.44 (n=19 | ) | 68.83 (n=85 | ) | 58.66 (n=23 | ) | ||||||||||
| 12 Months Mean CL 2 (OLE) | n/a | 78.86 (n=18 | ) | 61.60 (n=13 | ) | 52.88 (n=57 | ) | 27.47 (n=13 | ) |
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 ATTR amyloidosis with cardiomyopathy, 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 X (formerly Twitter) @ProthenaCorp.
Forward-Looking Statements
contains forward-looking statements. These statements relate to, among other things, the treatment potential, design, and proposed mechanism of action of our A -transferrin receptor antibody program; and our exploration of potential
partnership interest to advance our PRX012 and PRX012-TfR programs. 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 uncertainties related to the completion of operational and financial closing procedures, audit adjustments and other
developments that may arise that would require adjustments to the preliminary financial results included in this press release, as well as those described in the "Risk Factors" sections of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 4, 2025, 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.
Mark Johnson, CFA, Vice President, Investor