admilparant (BMS-986278) / BMS - LARVOL DELTA

Targeting Autotaxin and LPA in Pulmonary Fibrosis: Admilparant's Positive Results Show Continued Promise. (PubMed, Am J Respir Crit Care Med) - No abstract available

Journal • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Extent of Drug Interaction Between BMS-986278 and Ninetedanib, the Relative Bioavailability of BMS-986278 in Tablet and the Effect That Food Has on BMS-986278 in Tablet Formulations in Healthy Participants (clinicaltrials.gov) - P1 | N=73 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

Efficacy and Safety of Admilparant, an LPA1 Antagonist in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial. (PubMed, Am J Respir Crit Care Med) - P2 | "In this first phase 2 study to evaluate antifibrotic treatment in parallel IPF and PPF cohorts, 60-mg admilparant slowed lung function decline and was safe and well tolerated, supporting further evaluation in phase 3 trials. Clinical trial registration available at www."

Clinical • Journal • P2 data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

BAYESIAN APPROACH FOR ELEVATE IPF: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE EFFICACY, SAFETY, AND DOSE RESPONSE OF DEUPIRFENIDONE (LYT-100) IN IPF (CHEST 2024) - "There is precedent for leveraging Bayesian methodology in IPF studies (i.e., phase 2 programs for BI 1015550 and BMS-986278) to minimize the number of patients exposed to placebo while still generating data sufficient for decision making in drug development...The study will evaluate approximately 240 treatment-naïve adult participants, or those with less than 6 months exposure to nintedanib, at least 40 years of age at approximately 120 study centers globally... The Bayesian dynamic borrowing approach leverages the plethora of placebo data available from prior IPF studies. This approach has the potential to significantly enhance the statistical power of this study while limiting the number of patients required to be treated with placebo. CLINICAL IMPLICATIONS: Bayesian dynamic borrowing allows for historic IPF controls to complement clinical trial data to maximize the number of patients exposed to active treatment arms and minimize the number exposed to placebo."

Clinical • Idiopathic Pulmonary Fibrosis • Immunology • Oncology • Rare Diseases

A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=1092 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=1185 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Admilparant Affects Biomarkers in Pulmonary Fibrosis (Medscape) - "Additional research is needed, but the current results suggest that the biomarkers in patients with IPF and PFF may be used to monitor treatment response and disease progression in future trials for pulmonary fibrosis treatments, Maher said in his presentation."

Biomarker • Media quote • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Effects of lysophosphatidic acid receptor 1 (LPA1) antagonism on biomarkers in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF): data from a randomized phase 2 trial with BMS-986278 (ERS 2024) - P2 | "Treatment with BMS-986278 over 26 weeks significantly improved biomarkers of epithelial injury and fibrosis in patients with IPF, and biomarkers of inflammation and fibrosis in patients with PPF, consistent with effective antagonism of the LPA1 pathway."

Biomarker • Clinical • P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CHI3L1 • MMP7 • POSTN • TGFB1 • VCAM1

Emerging pharmacological options in the treatment of idiopathic pulmonary fibrosis (IPF). (PubMed, Expert Rev Clin Pharmacol) - "Currently, two agents, pirfenidone and nintedanib are approved for this disease, and both have been shown to reduce the rate of decline in lung function in patients with IPF...It is expected that the adverse drug effect profiles will be more favorable than current agents. It is further anticipated that these new agents or combinations of agents will arrest the fibrosis, not just slow the fibrotic process."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Extent of Drug Interaction Between BMS-986278 and Ninetedanib, the Relative Bioavailability of BMS-986278 in Tablet and the Effect That Food Has on BMS-986278 in Tablet Formulations in Healthy Participants (clinicaltrials.gov) - P1 | N=73 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

Evidence from recent clinical trials in fibrotic interstitial lung diseases. (PubMed, Curr Opin Pulm Med) - "Despite recent frustrating negative results, there is a growing portfolio of candidate drugs developed in both IPF and PPF."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CTGF

Sustainable manufacturing of BMS-986278 leveraging an ERED/KRED biocatalytic cascade (ACS-Fall 2024) - "The use of metric-based decision-making tools coupled with chemical innovation leading to a >8x improved yield while eliminating the use of halogenated solvents. The overall Process Mass Intensity (PMI) is reduced by 86% and projected raw material costs is lowered by 82%."

Concise approach to chiral cyclohexyl-based drug candidate BMS-986278 (ACS-Fall 2024) - "The route relies on an ene-reductase-keto-reductase reaction sequence to access a key chiral cyclohexyl fragment and a convergent Negishi coupling to assemble the biaryl core. BMS-986278 is synthesized in 6 steps over the longest linear sequence from commercially available material and is prepared on >250 kg scale."

Study to Assess Drug Levels and Safety of BMS-986278 in Healthy Participants and Participants With Different Degrees of Hepatic Impairment (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

Effect of BMS-986278, An Oral LPA1 Antagonist, on Time to Disease Progression in Patients With Pulmonary Fibrosis: A Post Hoc Analysis of Data From a Phase 2 Randomized Trial (ATS 2024) - P2 | "Consistent with the primary results, this analysis showed that BMS-986278 60 mg delayed time to disease progression over 26 weeks compared with placebo in patients with IPF."

Clinical • P2 data • Retrospective data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Assess Drug Levels and Safety of BMS-986278 in Healthy Participants and Participants With Different Degrees of Hepatic Impairment (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial • Hepatology

Peroxygenase-Catalyzed Allylic Oxidation Unlocks Telescoped Synthesis of (1S,3R)-3-Hydroxycyclohexanecarbonitrile. (PubMed, ACS Catal) - "Inspired by the discovery route toward the LPA1-antagonist BMS-986278, access to the API building block (1S,3R)-3-hydroxycyclohexanecarbonitrile was envisaged using an ene reductase (ER) and alcohol dehydrogenase (ADH) to set both stereocenters...After screening of enzyme panels, the final product was obtained at titers of 85% with 97% ee and 99% de, with a substrate loading of 50 mM, the ER being the limiting step. This synthetic approach provides the first example of a three-step, one-pot UPO-ER-ADH cascade and highlights the potential for UPOs to catalyze diverse enantioselective allylic hydroxylations and oxidations that are otherwise difficult to achieve."

Journal

A Study to Investigate the Effects of BMS-986278 on Drospirenone and Ethinyl Estradiol Drug Levels in Healthy Female Participants (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=1185 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P3 trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Effect of Multiple Doses of Itraconazole, Gemfibrozil, or Carbamazepine on BMS-986278 in Healthy Participants (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

A Study Measuring the Effectiveness, Safety, and Tolerability of BMS-986278 in Participants With Lung Fibrosis (clinicaltrials.gov) - P2 | N=399 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | N=278 ➔ 399

Enrollment change • Trial completion • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Bristol Myers Squibb Announces U.S. FDA Breakthrough Therapy Designation for Investigational LPA1 Antagonist for Progressive Pulmonary Fibrosis (Businesswire) - "Bristol Myers Squibb...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for BMS-986278, a potential first-in-class, oral, lysophosphatidic acid receptor 1 (LPA1) antagonist, for the treatment of progressive pulmonary fibrosis (PPF), a devastating, life-threatening illness....The Breakthrough Therapy Designation is based on results from the global, randomized Phase 2 study that assessed the safety and efficacy of BMS-986278 treatment versus placebo in people living with idiopathic pulmonary fibrosis (IPF) and PPF."

Breakthrough therapy designation • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

A Study to Investigate the Effects of BMS-986278 on Drospirenone and Ethinyl Estradiol Drug Levels in Healthy Female Participants (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Assess the Effect of Multiple Doses of Itraconazole, Gemfibrozil, or Carbamazepine on BMS-986278 in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

Phase 2 Study Results for Agents That Target LPA1 & JNK1 in Pulmonary Fibrosis (IPF Summit 2023) - "Synopsis Comparing BMS-986278 (LPA1 antagonist) and CC-90001 (JNK1 inhibitor) programs in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF): scientific rationale; study designs Key results from BMS-986278 and CC-90001 phase 2 trials Looking to phase 3 for the LPA1 program"

P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • MAPK8