Delving into the Latest Updates on Udifitimod with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Udifitimod Hydrochloride

+ [2]

Target

S1PR1

Mechanism

S1PR1 modulators(Sphingosine 1-phosphate receptor Edg-1 modulators)

Therapeutic Areas

Immune System DiseasesCongenital DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

Colitis, UlcerativeModerate Atopic DermatitisSevere Atopic Dermatitis

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.

Inactive Organization-

Drug Highest PhaseIND Application

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H33NO2

InChIKeyQCMHGCDOZLWPOT-FMNCTDSISA-N

CAS Registry1883345-06-9

AbstractSphingosine‐1‐phosphate (S1P) binding to the S1P‐1 receptor (S1P1R) controls the egress of lymphocytes from lymphoid organs and targets modulation of immune responses in autoimmune diseases. Pharmacologic modulation of S1P receptors has been linked to heart rate reduction. BMS‐986166, a prodrug of the active phosphorylated metabolite BMS‐986166‐P, presents an improved cardiac safety profile in preclinical studies compared to other S1P1R modulators. The pharmacokinetics, safety, and pharmacodynamics of BMS‐986166 versus placebo after single (0.75–5.0 mg) and repeated (0.25–1.5 mg/day) oral administration were assessed in healthy participants after a 1‐day lead‐in placebo period. A population model was developed to jointly describe BMS‐986166 and BMS‐986166‐P pharmacokinetics and predict individual exposures. Inhibitory sigmoid models described the relationships between average daily BMS‐986166‐P concentrations and nadir of time‐matched (day –1) placebo‐corrected heart rate on day 1 (nDDHR, where DD represents ∆∆) and nadir of absolute lymphocyte count (nALC). Predicted decreases in nDDHR and nALC were 9 bpm and 20% following placebo, with maximum decreases of 10 bpm in nDDHR due to drug effect, and approximately 80% in nALC due to drug and placebo. A 0.5‐mg/day dose regimen achieves the target 65% reduction in nALC associated with a 2‐bpm decrease in nDDHR over placebo.

02 Apr 2020·Expert Opinion on Investigational DrugsQ2 · MEDICINE

The safety and pharmacokinetics of a novel, selective S1P1R modulator in healthy participants

Q2 · MEDICINE

Article

Author: Girgis, Ihab G. ; Singhal, Shalabh ; Dutta, Santanu ; Shevell, Diane E. ; Throup, John ; Xie, Jenny

Background: Safety, pharmacokinetics and pharmacodynamics of BMS-986166, a novel sphingosine-1-phosphate receptor 1 modulator, were assessed.Research design and methods: Two double-blind, placebo-controlled, randomized Phase l studies were conducted in healthy participants. In the single ascending dose study (N = 70), BMS-986166 was administered as a single dose, upwardly titrated daily doses or a single dose in participants who were fed, fasted or administered famotidine. In the multiple ascending dose study (N = 32), BMS-986166 was administered daily for 28 days. Safety, pharmacokinetics and pharmacodynamics (absolute lymphocyte count [ALC]) were assessed.Results: BMS-986166 was generally well tolerated; treatment-related adverse events were mild. Dose-related, clinically insignificant reductions in time-matched heart rate were recorded versus placebo. Pharmacokinetics were linear and stationary with approximately dose-related increases in blood exposure of BMS-986166. Decreases in ALC percent change from baseline with multiple doses of BMS-986166 versus placebo were dose-related. Between Day 0 and 35, median nadir lymphocyte reductions were 53.7%, 75.9% and 81.9% with 0.25-, 0.75- and 1.5-mg BMS-986166 doses. ALC recovery began 14, 14-21 and 7 days after last dose of 0.25, 0.75 and 1.5 mg.Conclusions: BMS-986166 was generally well tolerated in this population and warrants further investigation.Trial registration: ClinicalTrials.gov: NCT02790125, NCT03038711.

14 Mar 2019·Journal of Medicinal ChemistryQ1 · MEDICINE

Identification and Preclinical Pharmacology of ((1R,3S)-1-Amino-3-((S)-6-(2-methoxyphenethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986166): A Differentiated Sphingosine-1-phosphate Receptor 1 (S1P₁) Modulator Advanced into Clinical Trials

Q1 · MEDICINE

Article

Author: Wu, Dauh-Rurng ; Shen, Ding Ren ; Salter-Cid, Luisa M. ; Mathur, Arvind ; Levesque, Paul C. ; Zhou, Xia D. ; Cvijic, Mary Ellen ; Dyckman, Alaric J. ; Yang, Michael G. ; Taylor, Tracy L. ; Warrack, Bethanne M. ; Chen, Cliff ; Carter, Percy H. ; Li, Yuwen ; Xie, Jenny ; Shi, Hong ; Heimrich, Elizabeth M. ; Marino, Anthony M. ; Thomas, Rochelle ; Xiao, Hai-Yun ; Gupta, Anuradha ; Gilmore, John L. ; Lehman-McKeeman, Lois D. ; Dhar, T. G. Murali ; Gong, Lei ; Borowski, Virna ; D’Arienzo, Celia J. ; Yang, Zheng ; Yang, Xiaoxia ; Lecureux, Lloyd ; Rampulla, Richard ; Sun, Huadong ; Xiao, Zili ; McIntyre, Kim W. ; Pragalathan, Bala ; Dabros, Marta ; Cornelius, Georgia

Recently, our research group reported the identification of BMS-986104 (2) as a differentiated S1P₁ receptor modulator. In comparison to fingolimod (1), a full agonist of S1P₁ currently marketed for the treatment of relapse remitting multiple sclerosis (RRMS), 2 offers several potential advantages having demonstrated improved safety multiples in preclinical evaluations against undesired pulmonary and cardiovascular effects. In clinical trials, 2 was found to exhibit a pharmacokinetic half-life ( T_1/2) longer than that of 1, as well as a reduced formation of the phosphate metabolite that is required for activity against S1P₁. Herein, we describe our efforts to discover highly potent, partial agonists of S1P₁ with a shorter T_1/2 and increased in vivo phosphate metabolite formation. These efforts culminated in the discovery of BMS-986166 (14a), which was advanced to human clinical evaluation. The pharmacokinetic/pharmacodynamic (PK/PD) relationship as well as pulmonary and cardiovascular safety assessments are discussed. Furthermore, efficacy of 14a in multiple preclinical models of autoimmune diseases are presented.

100 Deals associated with Udifitimod

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Moderate Atopic Dermatitis	Discovery	CA	Bristol Myers Squibb Co.	17 Aug 2021
Moderate Atopic Dermatitis	Discovery	US	Bristol Myers Squibb Co.	17 Aug 2021
Moderate Atopic Dermatitis	Discovery	PL	Bristol Myers Squibb Co.	17 Aug 2021
Moderate Atopic Dermatitis	Discovery	ES	Bristol Myers Squibb Co.	17 Aug 2021
Moderate Atopic Dermatitis	Discovery	AU	Bristol Myers Squibb Co.	17 Aug 2021
Moderate Atopic Dermatitis	Discovery	DE	Bristol Myers Squibb Co.	17 Aug 2021
Moderate Atopic Dermatitis	Discovery	AT	Bristol Myers Squibb Co.	17 Aug 2021
Severe Atopic Dermatitis	Discovery	AT	Bristol Myers Squibb Co.	17 Aug 2021
Severe Atopic Dermatitis	Discovery	PL	Bristol Myers Squibb Co.	17 Aug 2021
Severe Atopic Dermatitis	Discovery	AU	Bristol Myers Squibb Co.	17 Aug 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05014438 (CTgov)	Phase 2	Moderate Atopic Dermatitis \| Severe Atopic Dermatitis	17	Placebo	bgmimkbsxx(gtxctifsmy) = luklfuajeu kqiipzqzxp (zfifvjlpog, gtgzomppli - btojhjtmbk) View more	-	18 Oct 2023