BMS-986446 / Prothena, BMS - LARVOL DELTA

Updates on Active Clinical Development Portfolio:…BMS-986446 (formerly PRX005) (Businesswire) - "(i) Bristol Myers Squibb is conducting the Phase 2 TargetTau-1 clinical trial in approximately 310 patients with early Alzheimer’s disease; primary completion expected in 1H 2027 (NCT06268886); (ii) Bristol Myers Squibb is also conducting a Phase 1 open-label single-dose clinical trial to assess a subcutaneous administration; primary completion expected in 2H 2025 (NCT06955741)."

Trial primary completion date • Alzheimer's Disease

Bristol Myers Squibb…announced Wednesday that the U.S. Food and Drug Administration has granted Fast Track Designation to BMS-986446, its anti-microtubule binding region-tau (anti-MTBR-tau) antibody being developed for early Alzheimer’s disease (Investing.com) - "BMS-986446 is currently in Phase 2 clinical trials....The company reported that a Phase 1 study in healthy participants showed the drug was safe and well-tolerated across three dose cohorts."

Fast track • Alzheimer's Disease

A Study to Assess Drug Levels, Tolerability and Absolute Biological Availability of Single-dose of BMS-986446 in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed

Trial completion

A Study to Assess Drug Levels, Tolerability and Absolute Biological Availability of Single-dose of BMS-986446 in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed

Second Quarter, Recent Business Highlights and Upcoming Milestones (Businesswire) - "Partner Roche to advance prasinezumab into Phase 3 development for early-stage Parkinson's disease with initiation expected by the end of 2025...Roche has stated that prasinezumab has peak sales potential greater than $3 billion (unadjusted) and could be the first disease-modifying treatment for a condition that affects 10 million people worldwide...Prothena expects initial data in August from the Phase 1 ASCENT clinical trials....Bristol Myers Squibb is conducting the Phase 2 TargetTau-1 clinical trial in approximately 310 patients with early Alzheimer’s disease; primary completion expected in 2027 (NCT06268886); Bristol Myers Squibb is also conducting a Phase 1 open-label single-dose clinical trial to assess a subcutaneous administration; primary completion expected in 2H 2025 (NCT06955741)."

New P3 trial • P1 data • Sales • Trial primary completion date • Alzheimer's Disease • Parkinson's Disease

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=310 | Recruiting | Sponsor: Bristol-Myers Squibb | N=475 ➔ 310

Enrollment change • Alzheimer's Disease • CNS Disorders

A Study to Assess Drug Levels, Tolerability and Absolute Biological Availability of Single-dose of BMS-986446 in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

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

A Study to Assess Drug Levels, Tolerability and Absolute Biological Availability of Single-dose of BMS-986446 in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

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