BMS-986446 / Prothena, BMS - LARVOL DELTA

TargetTau-1: Study to Evaluate the Efficacy, Safety, and Tolerability of an Anti-MTBR Tau Monoclonal Antibody (BMS-986446) in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=475 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Aug 2027 ➔ Apr 2027

Trial primary completion date • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - P2 | "The phase 2 TargetTau-1 trial will assess efficacy, safety, and tolerability of BMS-986446, an anti-MTBR tau monoclonal antibody, in patients with early AD. References: 1. Horie K et al. Nat Med 2023;29:1954-1963. 2. Nolan P et al. Poster presented at the ADII; June 9-11, 2022; London, United Kingdom."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • MAPT

BMS begins domestic phase 2 clinical trials of Alzheimer’s drug candidate purchased for 183 billion won [Google translation] (Nate) - "According to the Ministry of Food and Drug Safety on the 11th, BMS Korea, the Korean subsidiary of BMS, recently received approval for a phase 2 clinical trial plan to evaluate the efficacy and safety of BMS-986446 for patients with early-stage Alzheimer's disease. This clinical trial is part of the global phase 2 clinical trial (clinical name TargetTau-1)...This clinical trial is scheduled to end in November 2027."

Trial completion date • Trial status • Alzheimer's Disease • CNS Disorders

Prothena Reports Third Quarter 2024 Financial Results and Business Highlights (Businesswire) - "BMS-986446...Bristol Myers Squibb continues to enroll the ongoing Phase 2 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 in 2025."

New P1 trial • Trial primary completion date • Alzheimer's Disease • CNS Disorders

TargetTau-1: A phase 2 trial designed to evaluate the efficacy, safety, and tolerability of the anti-MTBR tau monoclonal antibody, BMS-986446, in patients with early Alzheimer's disease (CTAD 2024) - No abstract available

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

TargetTau-1: Design of a phase 2 trial to evaluate the efficacy, safety, and tolerability of BMS-986446, an anti-MTBR tau monoclonal antibody, in patients with early Alzheimer's disease (AAIC 2024) - P2 | "The phase 2 TargetTau-1 trial will assess efficacy, safety, and tolerability of BMS-986446, an anti-MTBR tau monoclonal antibody, in patients with early AD."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • MAPT

A Study to Evaluate the Safety, Tolerability and Drug Levels of BMS-986446 in Healthy Participants and Healthy Participants of Japanese Ethnicity (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed

Trial completion

TargetTau-1: Study to Evaluate the Efficacy, Safety, and Tolerability of an Anti-MTBR Tau Monoclonal Antibody (BMS-986446) in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=475 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2027 ➔ Nov 2027 | Trial primary completion date: Mar 2027 ➔ Aug 2027

Enrollment open • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

TargetTau-1: Study to Evaluate the Efficacy, Safety, and Tolerability of an Anti-MTBR Tau Monoclonal Antibody (BMS-986446) in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=475 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P2 trial • Alzheimer's Disease • CNS Disorders

A Study to Evaluate the Safety, Tolerability and Drug Levels of BMS-986446 in Healthy Participants and Healthy Participants of Japanese Ethnicity (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

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

A Study to Evaluate the Safety, Tolerability and Drug Levels of BMS-986446 in Healthy Participants and Healthy Participants of Japanese Ethnicity (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

PRX005, a novel anti-MTBR tau monoclonal antibody: results from a first-in-human double-blind, placebo-controlled, single ascending dose phase 1 study (AAIC 2023) - "In this first-in-human, single ascending dose study, PRX005 was well tolerated and achieved CNS concentrations for pharmacological targeting of MTBR-tau. Our results support the progression of the clinical development of PRX005 in an ongoing, multiple ascending dose study in patients with Alzheimer’s disease."

Clinical • P1 data • 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) - "Prothena Corporation...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....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."

P1 data • Alzheimer's Disease • CNS Disorders • Tauopathies And Synucleinopathies

Prothena Announces Bristol Myers Squibb Opt-in for Worldwide Rights of PRX005, a Novel Anti-MTBR-Tau Antibody (Businesswire) - "Prothena Corporation...announced that Bristol Myers Squibb exercised its option under the global neuroscience research and development collaboration to obtain the exclusive worldwide commercial rights for PRX005 and will pay Prothena $55 million. PRX005, which is designed to be a best-in-class anti-tau antibody, specifically targets an area within the microtubule binding region (MTBR) of tau for the potential treatment of Alzheimer’s disease."

M&A • 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

Clinical Development of Passive Tau-Based Immunotherapeutics for Treating Primary and Secondary Tauopathies. (PubMed, Expert Opin Investig Drugs) - "At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

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

Prothena Reports Topline Phase 1 Single Ascending Dose Study Results of PRX005, a Novel Anti-MTBR-Tau Antibody for the Potential Treatment of Alzheimer’s Disease (GlobeNewswire) - P1 | N=19 | "Prothena Corporation...announced positive topline Phase 1 single ascending dose (SAD) study results for PRX005, a potentially best-in-class investigational tri-epitopic antibody for the treatment of Alzheimer’s disease 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....These topline Phase 1 data, together with the mounting scientific evidence suggesting that tau propagation could be mediated by MTBR-tau seeds, underscores the potential of PRX005 in treating Alzheimer’s disease....These results support the ongoing Phase 1 MAD trial of PRX005 in patients with Alzheimer’s disease. Topline results from the Phase 1 MAD trial are expected by year end 2023."

P1 data • Alzheimer's Disease • CNS Disorders

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 (PRTA) Stock Gains 51% in a Year: What Lies Ahead? (Yahoo Finance) - “The FDA recently cleared the investigational new drug (IND) application for Prothena’s PRX012…The company expects to initiate the phase I multiple ascending dose study by year-end 2022. Prothena is advancing an early-stage pipeline of programs for a number of potential neurological indications with Bristol Myers BMY. This includes PRX005 — a potential treatment for AD…A phase I study was initiated in 2021, and top-line data is expected in 2022. The company is also developing a dual Aβ-Tau vaccine…An IND for the vaccine is anticipated in 2023.”

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

Prothena Reports Fourth Quarter and Full Year 2021 Financial Results, and Provides Financial Guidance and Business Highlights (GlobeNewswire) - "PRX012, Investigational New Drug (IND) application filing expected 1Q 2022....PRX005, Topline Phase 1 data expected in 2022."

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

"@ProthenaCorp has tau programs too: PRX005 partnered with @bmsnews and wholly-owned Dual abeta-tau vaccine) #truestory 😳" (@tranbryannguyen)

Clinical

Prothena Announces Bristol Myers Squibb Opt-in of Anti-Tau PRX005 as the First Program from Global Neuroscience Research and Development Collaboration (GlobeNewswire) - "Prothena Corporation...today announced that Bristol Myers Squibb exercised its option under the global neuroscience research and development collaboration to enter into an exclusive U.S. license for PRX005 and will pay Prothena $80 million....Phase 1 study with PRX005 has initiated."

Licensing / partnership • Trial status • Alzheimer's Disease • CNS Disorders

Prothena Reports First Quarter 2021 Financial Results and Provides Updated Financial Guidance and R&D Update (GlobeNewswire) - "Upcoming Milestones: Birtamimab: Phase 3 AFFIRM-AL study initiation expected mid-2021...Prasinezumab: Results from Part 2 of the PASADENA study expected to be presented at an upcoming medical conference...PRX004: Phase 2/3 study in patients with ATTR-cardiomyopathy expected to initiate 4Q 2021...PRX005: IND expected by 3Q 2021 $80 million potential payment from Bristol Myers Squibb upon exercising their US license option in 2021...PRX012, a potential treatment for Alzheimer’s disease...IND expected by 1Q 2022...Research and development (R&D) expenses totaled $21.1 million for the first quarter of 2021..."

Commercial • Financing • IND • New P2/3 trial • New P3 trial • P2 data • Alzheimer's Disease • Amyloidosis • CNS Disorders • Frontotemporal Lobar Degeneration • Parkinson's Disease • Progressive Supranuclear Palsy • Tauopathies And Synucleinopathies