BMS-986196 / BMS - LARVOL DELTA

Discovery of BMS-986196: A brain-penetrant, covalent inhibitor providing rapid inactivation of Bruton's Tyrosine Kinase (BTK) (ACS-Fall 2025) - "This presentation will outline the evolution of our strategy to identify a brain-penetrant, covalent inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically and in the CNS to treat patients with MS. With in vivo efficacy, a desirable tolerability profile, and pre-clinical target engagement in the brain confirmed by PET imaging, BMS-986196 advanced into clinical studies."

CNS Disorders • Inflammation • Multiple Sclerosis • BTK

A Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution and Repeatability of 11C-BMS-986196 After Intravenous (IV) Administration in Healthy Participants and After Repeat IV Administration in Participants With Multiple Sclerosis (clinicaltrials.gov) - P1 | N=10 | Terminated | Sponsor: Bristol-Myers Squibb | Completed ➔ Terminated; Business objectives have changed

Trial termination • CNS Disorders • Multiple Sclerosis

A Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution and Repeatability of 11C-BMS-986196 After Intravenous (IV) Administration in Healthy Participants and After Repeat IV Administration in Participants With Multiple Sclerosis (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ Dec 2023 | Trial primary completion date: Aug 2024 ➔ Dec 2023

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution and Repeatability of 11C-BMS-986196 After Intravenous (IV) Administration in Healthy Participants and After Repeat IV Administration in Participants With Multiple Sclerosis (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2023 ➔ Aug 2024 | Trial primary completion date: Jul 2023 ➔ Aug 2024

Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study to Evaluate the Drug Levels, Physical and Chemical Changes, and Removal of BMS-986196 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

A Phase 1 Study of the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986196, an Oral CNS-penetrant BTK Inhibitor, in Healthy Adults (MSMilan 2023) - "BMS-986196 was safe and tolerated at all dose levels in this study. Taken together, the safety, pharmacokinetic and BTK occupancy results support future clinical studies of BMS-986196."

Clinical • P1 data • PK/PD data • CNS Disorders • Multiple Sclerosis

A Study to Evaluate the Drug-drug Interaction Potential of BMS-986196 in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

A Study to Evaluate the Drug-drug Interaction of BMS-986196 With Oral Contraceptives in Healthy Female Participants (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

A Study to Evaluate the Drug Levels, Physical and Chemical Changes, and Removal of BMS-986196 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Effect of Food on the Drug Levels of BMS-986196 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

A Study to Evaluate the Effect of Food on the Drug Levels of BMS-986196 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Withdrawn

Trial withdrawal

A Study to Evaluate the Drug Levels, Physical and Chemical Changes, and Removal of BMS-986196 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

A Study to Evaluate the Drug-drug Interaction of BMS-986196 With Oral Contraceptives in Healthy Female Participants (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Drug-drug Interaction Potential of BMS-986196 in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Drug-drug Interaction of BMS-986196 With Oral Contraceptives in Healthy Female Participants (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

A Study to Evaluate the Drug-drug Interaction Potential of BMS-986196 in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

A Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution and Repeatability of 11C-BMS-986196 After Intravenous (IV) Administration in Healthy Participants and After Repeat IV Administration in Participants With Multiple Sclerosis (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Mar 2023 ➔ Jul 2023 | Trial primary completion date: Mar 2023 ➔ Jul 2023

Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution and Repeatability of 11C-BMS-986196 After Intravenous (IV) Administration in Healthy Participants and After Repeat IV Administration in Participants With Multiple Sclerosis (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2022 ➔ Mar 2023 | Trial primary completion date: Jul 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study to Determine the Safety, Drug Levels and Drug Effects of BMS-986196 and Food and Formulation Effects on Relative Absorption Healthy Participants (clinicaltrials.gov) - P1 | N=102 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

A Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution and Repeatability of 11C-BMS-986196 After Intravenous (IV) Administration in Healthy Participants and After Repeat IV Administration in Participants With Multiple Sclerosis (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2022 ➔ Jul 2022 | Trial primary completion date: Mar 2022 ➔ Jul 2022

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study to Determine the Safety, Drug Levels and Drug Effects of BMS-986196 and Food and Formulation Effects on Relative Absorption Healthy Participants (clinicaltrials.gov) - P1 | N=102 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open