PRX012 / Prothena - LARVOL DELTA

Prothena Announces Corporate Restructuring (Businesswire) - "Company expects initial data in August from Phase 1 ASCENT clinical trials of its wholly owned PRX012 program in Alzheimer’s disease; Novo Nordisk expects to share data from its Phase 2 clinical trial evaluating coramitug for ATTR-CM in the second half of 2025; Company expects to complete a Phase 1 clinical trial for PRX019 in collaboration with Bristol Myers Squibb in 2026."

Clinical data • Trial status • Alzheimer's Disease • Amyloidosis • Cardiomyopathy

Prothena Reports First Quarter 2025 Financial Results and Business Highlights (Businesswire) - "PRX012: Prothena expects to report multiple clinical readouts starting around mid-2025 and continuing throughout the year from the ongoing Phase 1 ASCENT clinical trials. Prothena has currently enrolled approximately 260 patients in the ASCENT clinical trials BMS-986446 (formerly PRX005): Bristol Myers Squibb continues to enroll the ongoing Phase 2 Target Tau-1 clinical trial in approximately 475 patients with early Alzheimer’s disease; primary completion expected in 2027 (NCT06268886)....PRX123: Continuing to optimize capital allocation across our robust R&D pipeline, Prothena expects to update plans for Phase 1 clinical trial by year-end 2025....Prasinezumab: Roche will continue to evaluate data from PADOVA and will work together with health authorities to determine next steps around mid-year 2025."

New P1 trial • P1 data • P2b data • Trial completion date • Alzheimer's Disease • Parkinson's Disease

ACCURACY OF PLASMA BIOMARKERS FOR DETECTING AMYLOID BETA DEPOSITS IN PARTICIPANTS WITH ALZHEIMER'S DISEASE IN ASCENT-2 CLINICAL TRIAL OF PRX012 (ADPD 2025) - "ptau217 had the highest accuracy at predicting Aβ-PET positivity. These Results suggest that ptau217 prescreening could decrease the need for Aβ-PET testing, supporting the use of AD plasma biomarkers as minimally invasive tools for clinical trial prescreening."

Biomarker • Clinical • Alzheimer's Disease • CNS Disorders • Aβ42 • p-tau181

Accuracy of Plasma Biomarkers for Detecting Amyloid Beta Deposits in Participants With Alzheimer's Disease in ASCENT-2 Clinical Trial of PRX012 (AAN 2025) - "ROC values for the evaluated biomarkers were consistent with those previously reported. ptau217 had the highest accuracy at predicting Aβ-PET positivity. These results suggest that ptau217 prescreening could decrease the need for Aβ-PET testing, supporting the use of AD plasma biomarkers as minimally invasive tools for clinical trial prescreening."

Biomarker • Clinical • Alzheimer's Disease • CNS Disorders • Aβ42 • p-tau181

Drug Development. (PubMed, Alzheimers Dement) - "Phase 1 development of PRX012 will support future late-stage clinical trials that have the potential to position PRX012 as a best-in-class, next-generation once-monthly subcutaneous antibody for the treatment of AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry • APOE

Prothena Reports Third Quarter 2024 Financial Results and Business Highlights (Businesswire) - "'From our wholly-owned programs we expect to complete our confirmatory Phase 3 AFFIRM-AL clinical trial evaluating birtamimab, which is being conducted under a SPA agreement with the FDA at a significance level of 0.10, in 1H 2025. We also expect to announce multiple clinical readouts from our ongoing Phase 1 ASCENT clinical trials evaluating PRX012 for Alzheimer’s disease starting in mid-2025 and continuing throughout the year. In collaboration with Roche, we expect results from the Phase 2b PADOVA clinical trial evaluating prasinezumab for Parkinson’s disease in 4Q 2024 and with Novo Nordisk, we expect results from the Phase 2 signal-detection clinical trial evaluating coramitug for ATTR amyloidosis with cardiomyopathy in 1H 2025.'"

P1 data • P2 data • P2b data • Trial completion • Alzheimer's Disease • Amyloidosis • CNS Disorders • Metabolic Disorders • Parkinson's Disease

Increasing Representation and Diversity in Clinical Trials of Alzheimer's Disease: Recruitment of Ethnically Diverse Participants with Alzheimer's Disease in the Phase 1 ASCENT Clinical Trials of PRX012 (CTAD 2024) - No abstract available

Clinical • P1 data • Alzheimer's Disease • CNS Disorders

Binding characteristics of PRX012 surrogate demonstrate potent engagement of toxic amyloid beta protofibrils and robust clearance of pyroglutamate-modified amyloid beta (AEC 2024) - "Background: Multiple clinical trials evaluating first-generation anti-Aβ mAbs (aducanumab, lecanemab, donanemab) show that Aβ plaque reduction is associated with slowing clinical decline in AD. PRX012s, an N-terminal-targeted anti-Aβ mAb, demonstrated superior binding to protofibrils and phagocytic clearance of pyroglutamate-modified Aβ when compared with lecanemab and donanemab, respectively. These data further support the ongoing clinical development of PRX012 as a potential best-in-class anti-Aβ immunotherapy that could enable a low-volume, infrequent subcutaneous injectable to reduce barriers to treatment."

Alzheimer's Disease • CNS Disorders

Phase 1 Single and Multiple Dose Clinical Trials (ASCENT-1 and ASCENT-2) for Dose-Finding of PRX012 in Participants with Biologically Confirmed Alzheimer’s Disease (AAIC 2024) - "Phase 1 development of PRX012 will support future late-stage clinical trials that have the potential to position PRX012 as a best-in-class, next-generation once-monthly subcutaneous antibody for the treatment of AD."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry • APOE

Prothena Reports First Quarter 2024 Financial Results and Business Highlights (Businesswire) - "The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PRX012 for the treatment of Alzheimer’s disease....Phase 1 clinical trial continues as planned and expect to update in 2024...The FDA cleared the investigational new drug (IND) application and granted Fast Track designation for PRX123 for the treatment of Alzheimer’s disease."

Fast track designation • IND • New trial • P1 data • Alzheimer's Disease • CNS Disorders

Binding Characteristics of PRX012 Surrogate Demonstrate Potent Engagement of Toxic Amyloid Beta Protofibrils and Robust Clearance of Pyroglutamate-modified Amyloid Beta (AAN 2024) - "Objective:To build a more detailed understanding of the biological activity and binding interactions of PRX012, a next-generation, subcutaneously delivered anti-amyloid-beta (Aβ) monoclonal antibody (mAb) under investigation for the treatment of Alzheimer's disease (AD).Background:Multiple clinical trials evaluating first-generation anti-Aβ mAbs (aducanumab, lecanemab, donanemab) show that Aβ plaque reduction closely correlates with slowing clinical decline in AD. PRX012s, an N-terminal-targeted anti-Aβ mAb, demonstrated superior binding to protofibrils and phagocytic clearance of pyroglutamate-modified Aβ when compared with lecanemab and donanemab, respectively. These data further support the ongoing clinical development of PRX012 as a potential best-in-class anti-Aβ immunotherapy that could enable a low-volume, infrequent subcutaneous injectable to reduce barriers to treatment."

Alzheimer's Disease • CNS Disorders

Prothena Provides Updates on PRX012, PRX123, Birtamimab and Portfolio Programs (Businesswire) - "PRX012...Ongoing Phase 1 trial continues as planned and expect to update in 2024....PRX123...Phase 1 timeline update expected in 2024 in order to optimize capital allocation across robust clinical portfolio..."

P1 data • Alzheimer's Disease • CNS Disorders

Prothena Reports Third Quarter 2023 Financial Results and Business Highlights (Businesswire) - P2 | N=312 | PASADENA (NCT03100149) | Sponsor: Hoffmann-La Roche | "PRX012...initial topline data expected by year-end 2023....Received $55 million payment from Bristol Myers Squibb for exclusive worldwide license to BMS-986446, optioned in July; Bristol Myers Squibb reported that Phase 1 data supports rapidly moving BMS-986446 into a Phase 2 clinical trial in first half 2024; PRX123....Investigational new drug (IND) application expected by year-end 2023....Roche presented data at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) from the open-label extension of the PASADENA study which shows that prasinezumab slowed the progression of motor deficits (MDS-UPDRS Part III OFF state score) in early-stage PD; Roche completed enrollment for the Phase 2b PADOVA clinical trial in patients with early PD (NCT04777331); topline results expected in 2024..."

Commercial • IND • New P2 trial • P1 data • P2 data • P2b data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Binding characteristics of PRX012 surrogate demonstrate potent engagement of toxic Aβ protofibrils and robust clearance of pyroglutamate-modified Aβ (AAIC 2023) - "Background: Multiple clinical trials evaluating first-generation anti-beta amyloid (Aβ) monoclonal antibodies (aducanumab, lecanemab, donanemab) show that Aβ plaque reduction closely correlates with slowing clinical decline in Alzheimer’s disease (AD). PRX012s, an N-terminal-targeted anti-Aβ mAb, demonstrated superior binding to protofibrils and phagocytic clearance of pyroglutamate-modified Aβ when compared with lecanemab and donanemab, respectively. These data further support the ongoing clinical development of PRX012 as a potential best-in-class anti-Aβ immunotherapy that could enable a low-volume, infrequent subcutaneous injectable to reduce barriers to treatment."

Alzheimer's Disease • CNS Disorders

Prothena Presents New Research in the Treatment of Alzheimer’s Disease at Alzheimer’s Association International Conference 2023 (AAIC) (Businesswire) - "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....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."

Preclinical • Alzheimer's Disease • CNS Disorders • Tauopathies And Synucleinopathies

Prothena to Present New Data from Alzheimer’s Disease Programs at Alzheimer’s Association International Conference 2023 (AAIC) (Businesswire) - "Prothena will highlight results in a poster presentation from a single ascending dose (SAD) study in healthy volunteers receiving PRX005...that specifically binds with high affinity to the R1, R2, and R3 repeats within the microtubule binding region (MTBR) of tau and targets both 3R and 4R tau isoforms....Prothena will present preclinical data in a late breaker poster presentation on the immunological response to the dual Aβ/Tau vaccine PRX123 surrogate and the effects on brain amyloid plaques in a rapidly depositing transgenic animal model....Prothena will present an encore poster presentation of data originally presented at the 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD) on preclinical data from the PRX012 program comparing a PRX012-surrogate1 (PRX012s) with lecanemab and donanemab."

Clinical data • Preclinical • Alzheimer's Disease • CNS Disorders • Tauopathies And Synucleinopathies

Walgreens and Prothena Partner to Increase Access and Enrollment in Alzheimer’s Disease Clinical Trial (Prothena Press Release) - "Walgreens and Prothena today announced a collaboration to accelerate patient identification and recruitment for Prothena’s ongoing ASCENT-2 multiple ascending dose clinical trial evaluating the safety and tolerability of PRX012, a potential best-in-class anti-amyloid beta antibody under development for the treatment of Alzheimer’s disease. As part of the collaboration, Walgreens will leverage its national footprint, portfolio of industry-leading healthcare companies and compliance framework to match patient populations to this Prothena clinical trial for PRX012, which has been granted Fast Track designation by the U.S. Food and Drug Administration....Prothena’s Phase 1 PRX012 single ascending dose (SAD) and multiple ascending dose (MAD) studies are ongoing with topline data expected year end 2023."

Fast track designation • Licensing / partnership • P1 data • Alzheimer's Disease • CNS Disorders

Prothena Presents New Preclinical Data Supporting Best-in-Class Profile of PRX012, a Next-Generation Anti-Amyloid Beta Antibody, at AD/PD 2023 (Businesswire) - "The second study, an ex vivo study using post-mortem Alzheimer’s disease brain tissue, was designed to test the ability of PRX012s to clear pyroglutamate-modified Aβ deposited in plaques. Study results showed that lower concentrations of PRX012s induced more potent and robust clearance of pyroglutamate-modified Aβ as compared to donanemab+. In the experiment, microglia simultaneously phagocytosed non-pyroglutamate-modified Aβ and pyroglutamate-modified Aβ in the presence of PRX012s, indicating that high opsonization efficiency of plaques by PRX012s was sufficient to clear both forms of Aβ."

Preclinical • Alzheimer's Disease • CNS Disorders

Prothena Presents New Preclinical Data Supporting Best-in-Class Profile of PRX012, a Next-Generation Anti-Amyloid Beta Antibody, at AD/PD 2023 (Businesswire) - "Surface Plasmon Resonance (SPR) was used to compare PRX012s to lecanemab+ and showed that PRX012s had approximately 20-fold higher affinity to Aβ 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."

Preclinical • Alzheimer's Disease • CNS Disorders

Prothena to Highlight Next Generation Treatments for Alzheimer’s and Parkinson’s Disease at the AD/PD 2023 Meeting (Businesswire) - “Oral presentation on PRX012, Prothena’s next generation anti-amyloid beta antibody for Alzheimer’s disease, demonstrates higher affinity binding to amyloid beta protofibrils and greater clearance of pyroglutamate-amyloid beta plaques compared to other approved and investigational molecules….Poster and Symposium presentations by partner Roche on Phase 2 PASADENA study of prasinezumab for Parkinson’s disease. Prothena Corporation plc…announced broad participation at the 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD) being held March 28 – April 1, 2023 in Gothenburg, Sweden, highlighting Prothena's leadership in advancing next generation treatments for Alzheimer’s and Parkinson’s disease.”

Clinical • Alzheimer's Disease • CNS Disorders • Parkinson's Disease • Tauopathies And Synucleinopathies

Prothena Reports Fourth Quarter and Full Year 2022 Financial Results, and Provides Financial Guidance and Business Highlights (Businesswire) - “PRX012: Significant presence at upcoming International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) in March/April 2023 highlighted by oral presentation of preclinical data showing superior binding characteristics of PRX012 and a symposium featuring key thought leaders. Ongoing Phase 1 SAD and MAD studies; topline data expected year end 2023….PRX005: Ongoing Phase 1 MAD study; topline data expected year end 2023. PRX123: Investigational new drug (IND) application filing expected by year end 2023….NNC6019: Ongoing Phase 2 study in patients with ATTR cardiomyopathy is being conducted by Novo Nordisk (NCT05442047); topline data expected in 2024.”

IND • P1 data • P2 data • Preclinical • Alzheimer's Disease • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • CNS Disorders

BINDING CHARACTERISTICS OF SURROGATE PRX012 DEMONSTRATE POTENT ENGAGEMENT OF TOXIC ABETA PROTOFIBRILS AND ROBUST CLEARANCE OF PYROGLUTAMATE-MODIFIED ABETA (ADPD 2023) - "Aims Multiple clinical trials evaluating first-generation anti-beta amyloid (Ab) monoclonal antibodies (aducanumab, lecanemab, donanemab) show that Ab plaque reduction correlates with slowing clinical decline in Alzheimer's disease (AD). Conclusions PRX012s, an N-terminal-targeted anti-Aβ mAb, demonstrated superior binding to protofibrils and phagocytic clearance of pyroglutamate-modified Aβ when compared with lecanemab and donanemab, respectively. These data further support the ongoing clinical development of PRX012 as a potential best-in-class anti-Aβ immunotherapy that could enable a low-volume, infrequent subcutaneous injectable to reduce barriers to treatment."

Alzheimer's Disease • CNS Disorders

INDUSTRY SYMPOSIUM 04 (NONE CME/CPD CREDIT) (ADPD 2023) - "This will include discussion of the emergence of PRX012, a novel anti-Aβ mAb designed for subcutaneous administration that potently binds Aβ and is currently being evaluated in a Phase 1 clinical trial by Prothena. Other investigational approaches, such as combination therapy with anti-Aβ mAbs, will also be discussed."

Alzheimer's Disease • CNS Disorders • APOE

Prothena Reports Third Quarter 2022 Financial Results and Business Highlights (Businesswire) - “Neurodegenerative Diseases Portfolio: Alzheimer’s Disease (AD): PRX012…Phase 1 multiple ascending dose (MAD) study initiation expected by year-end 2022; Topline data from Phase 1 study expected in 2023. PRX005…Topline data from Phase 1 study expected by year-end 2022; PRX123…IND filing expected in 2023….Research and development (R&D) expenses totaled $39.9 million and $98.7 million for the third quarter and first nine months of 2022, respectively, as compared to $18.0 million and $60.2 million for the third quarter and first nine months of 2021, respectively. The increase in R&D expense for the third quarter and first nine months of 2022 compared to the same periods in the prior year was primarily due to higher manufacturing costs primarily related to the birtamimab, PRX012, PRX019, PRX123 and PRX005 programs…”

Commercial • IND • New P1 trial • P1 data • Alzheimer's Disease • CNS Disorders

Prothena Reports Second Quarter 2022 Financial Results and Business Highlights (GlobeNewswire) - “Rare Peripheral Amyloid Diseases Portfolio: AL Amyloidosis: Birtamimab…Abstract accepted for poster presentation on Monday September 5, 2022 at the XVIII International Symposium on Amyloidosis (ISA) titled: Birtamimab in Patients with Mayo Stage IV AL Amyloidosis: Rationale for Confirmatory AFFIRM-AL Phase 3 Study (Poster P040). Confirmatory Phase 3 AFFIRM-AL study results expected in 2024….Research and development (R&D) expenses totaled $31.6 million and $58.8 million for the second quarter and first six months of 2022, respectively, as compared to $21.1 million and $42.2 million for the second quarter and first six months of 2021, respectively. The increase in R&D expense for the second quarter…was primarily due to higher personnel related expenses, higher clinical trial expenses primarily related to the PRX012 and birtamimab programs..."

Commercial • P3 data • Alzheimer's Disease • Amyloidosis • CNS Disorders