BMS-986446 / Prothena, BMS - LARVOL DELTA

RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETICS, AND IMMUNOGENICITY OF BMS-986446 IN HEALTHY PARTICIPANTS, INCLUDING THOSE OF JAPANESE ETHNICITY (ADPD 2026) - "Single-dose BMS-986446 was safe and well tolerated in all participants, including those of Japanese ethnicity. Plasma exposure of BMS-986446 increased dose proportionally. No anti-drug antibodies were detected."

Clinical • PK/PD data • Alzheimer's Disease • CNS Disorders

A first-in-human double-blind, placebo-controlled, multiple ascending dose phase 1 study evaluating the safety and pharmacokinetics of PRX005/BMS-986446, a novel anti-MTBR tau monoclonal antibody, in healthy adults and patients with Alzheimer's disease (CTAD 2025) - No abstract available

Clinical • First-in-human • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders

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