Delving into the Latest Updates on Funobactam with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

XNW-4107, XNW4107

Target

β-lactamase

Mechanism

β-lactamase inhibitors(Beta Lactamase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System DisordersRespiratory Diseases+ [1]

Active Indication

Acute pyelonephritisComplicated urinary tract infectionPancreatitis+ [3]

Inactive Indication-

Originator Organization

Evopoint Biosciences Co., Ltd.Startup

Active Organization

Evopoint Biosciences AU Pty Ltd

Evopoint Biosciences Co., Ltd.Startup

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC13H17N7O6S

InChIKeyGRRBXZJDEZJMHA-FXQIFTODSA-N

CAS Registry2365454-12-0

[Translation] A multicenter, randomized, double-blind, controlled phase III clinical study to evaluate the efficacy and safety of imipenem/cilastatin-XNW4107 for injection compared with imipenem/cilastatin/relebactam in the treatment of adult hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia

主要目的：评估IMI-XNW4107组与IMI/REL组相比，随机化后至D14，在MITT人群中的全因死亡率。次要目的 :1.有效性：评估IMI-XNW4107组与IMI/REL组相比，(1)随机化后至D28，在MITT人群中的全因死亡率。(2)随机化至D14和至D28，在micro-MITT，扩展micro-MITT，CE，ME和CR-MITT人群中的全因死亡率。(3)在D4，EOT，TOC和LFU时，在MITT，micro-MITT，扩展micro-MITT，CE，ME和CR-MITT人群中的临床疗效。(4)在EOT，TOC和LFU访视时，在micro-MITT，扩展的micro-MITT，ME和CR-MITT人群中的微生物学疗效。(5)在EOT，TOC和LFU访视时，在micro-MITT，扩展的micro-MITT，ME和CR-MITT人群中，按病原体分类的微生物学疗效(6)在EOT, TOC和LFU访视时，在micro-MITT，扩展的micro-MITT，ME和CR-MITT人群中的综合疗效。 2.安全性和耐受性。 3.药代动力学。探索性目的：医疗保健资源利用情况。

[Translation]

Primary Objectives: To evaluate all-cause mortality in the MITT population from randomization to D14 in the IMI-XNW4107 group compared with the IMI/REL group. Secondary Objectives: 1. Efficacy: To evaluate (1) all-cause mortality in the MITT population from randomization to D28 in the IMI-XNW4107 group compared with the IMI/REL group. (2) all-cause mortality in the micro-MITT, extended micro-MITT, CE, ME, and CR-MITT populations from randomization to D14 and to D28. (3) clinical efficacy at D4, EOT, TOC, and LFU in the MITT, micro-MITT, extended micro-MITT, CE, ME, and CR-MITT populations. (4) microbiological efficacy at the EOT, TOC, and LFU visits in the micro-MITT, extended micro-MITT, ME, and CR-MITT populations. (5) Microbiological efficacy by pathogen at EOT, TOC, and LFU visits in micro-MITT, extended micro-MITT, ME, and CR-MITT populations (6) Composite efficacy at EOT, TOC, and LFU visits in micro-MITT, extended micro-MITT, ME, and CR-MITT populations. 2. Safety and tolerability. 3. Pharmacokinetics. Exploratory objectives: Healthcare resource utilization.

Start Date31 Mar 2023

Sponsor / Collaborator

Evopoint Biosciences Co., Ltd.Startup

NCT05204368 / Not yet recruitingPhase 3

A Multicenter, Randomized, Double-Blind, Double-Dummy, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Meropenem in Hospitalized Adults With Complicated Urinary Tract Infections, Including Acute Pyelonephritis.(EudraCT no. 2022-000061-40)

This is A Multicenter, Randomized, Double-Blind, Double-Dummy, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/Funobactam in Comparison with Meropenem in Hospitalized Adults with Complicated Urinary Tract Infections, including Acute Pyelonephritis.

Start Date30 Mar 2023

Sponsor / Collaborator

Evopoint Biosciences AU Pty Ltd

NCT05204563 / RecruitingPhase 3

A Multicenter, Randomized, Double-Blind, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Imipenem/Cilastatin/Relebactam in Adults With Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia (EudraCT no. 2022-000081-18) (EUCTR no. 2022-501952-27-00) (IND no. 146614)

This study aims to compare treatment with Imipenem/Cilastatin-XNW4107 (IMI-XNW4107) with imipenem/cilastatin/relebactam (IMI/REL) in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or VAPB, respectively). The primary hypothesis is that IMI-XNW4107 is non-inferior to IMI/REL in all-cause mortality.

Start Date31 Jul 2022

Sponsor / Collaborator

Evopoint Biosciences AU Pty Ltd

100 Clinical Results associated with Funobactam

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100 Translational Medicine associated with Funobactam

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100 Patents (Medical) associated with Funobactam

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2

Literatures (Medical) associated with Funobactam

05 Sep 2023·The Journal of antimicrobial chemotherapy

Imipenem/funobactam (formerly XNW4107) in vivo pharmacodynamics against serine carbapenemase-producing Gram-negative bacteria: a novel modelling approach for time-dependent killing.

Article

Author: Fratoni, Andrew J ; Wu, Yuchuan ; Abdelraouf, Kamilia ; Liu, Xiao ; Chen, Xi ; Berry, Angela V ; Nicolau, David P

BACKGROUND:

Imipenem/funobactam (formerly XNW4107) is a novel β-lactam/β-lactamase inhibitor with activity against MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales strains. Using a neutropenic murine thigh infection model, we aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) index, relative to funobactam exposure, that correlated most closely with the in vivo efficacy of imipenem/funobactam combination and the magnitude of index required for efficacy against serine carbapenemase-producing clinical strains.

METHODS:

Dose-fractionation was conducted against three strains. Imipenem human-simulated regimen (HSR, 500 mg q6h 1 h infusion) efficacy in combination with escalating funobactam exposures against seven A. baumannii, four P. aeruginosa and four Klebsiella pneumoniae (imipenem/funobactam MICs 0.25-16 mg/L) was assessed as 24 h change in log10cfu/thigh.

RESULTS:

Increased funobactam fractionation enhanced efficacy, indicating time-dependent killing. Changes in log10cfu/thigh versus %fT > MIC were poorly predictive of efficacy; bactericidal activity was observed at %fT > MIC = 0%. Across different threshold plasma funobactam concentrations (CTs), %fT > CT(1 mg/L) had the highest correlation with efficacy. Normalizing the %fT > CT = 1 mg/L index to the respective isolate imipenem/funobactam MIC ([%fT > CT]/MIC) allowed integration of the isolate's susceptibility, which further enhanced the correlation. Median (%fT > CT[1 mg/L])/MIC values associated with 1-log reductions were 9.82 and 9.90 for A. baumannii and P. aeruginosa, respectively. Median (%fT > CT[1 mg/L])/MIC associated with stasis was 55.73 for K. pneumoniae. Imipenem/funobactam 500/250 mg q6h 1 h infusion HSR produced >1-log kill against 6/7 A. baumannii, 4/4 P. aeruginosa and stasis against 4/4 K. pneumoniae.

CONCLUSIONS:

Imipenem/funobactam showed potent in vivo efficacy against serine carbapenemase-producers. The novel PK/PD index (%fT > CT)/MIC appeared to best describe in vivo activity.

01 Dec 2022·Journal of global antimicrobial resistance

In vitro and in vivo activities of a novel β-lactamase inhibitor combination imipenem/XNW4107 against recent clinical Gram-negative bacilli from China

Article

Author: Wang, Qing ; Yan, Mengyao ; Liu, Xiao ; Lv, Yuan ; Zheng, Bo ; Chen, Xi ; Zhong, Wei ; Li, Yun ; Wu, Yuchuan ; Xue, Feng ; Zhang, Jia

OBJECTIVES:

XNW4107 is a novel β-lactamase inhibitor that possesses broad activity against serine-β-lactamases. XNW4107 in combination with imipenem exhibited potent in vitro activity against carbapenem-resistant bacteria and particularly against carbapenem-resistant Acinetobacter baumannii. This study aimed to evaluate the in vitro and in vivo antibacterial activities of imipenem/XNW4107.

METHODS:

The minimum inhibitory concentrations, minimum bactericidal concentrations, time-kill curves, post-antibiotic effects, and spontaneous frequency of resistance were used to investigate the imipenem/XNW4107 in vitro activity. A mouse systemic infection model was used to evaluate the imipenem/XNW4107 in vivo efficacy.

RESULTS:

MIC₉₀ of imipenem/XNW4107 against imipenem-nonsusceptible A. baumannii (n = 106) was 8 mg/L, which was 16-fold lower than the MIC₉₀ of imipenem; the resistance rate decreased from 90% to 20% applying the CLSI imipenem breakpoint. MIC₉₀ of imipenem/XNW4107 against imipenem-resistant Klebsiella pneumoniae (n = 54) was 2 mg/L, which was 128-fold lower than the MIC₉₀ of imipenem; 80% imipenem-nonsusceptible Pseudomonas aeruginosa (n = 101) exhibited MICs of imipenem/XNW4107 from 2 to 8 mg/L, which were 4- to 8-fold lower than the MICs of imipenem. Imipenem/XNW4107 was bactericidal against A. baumannii, K. pneumoniae, and Escherichia coli. The time-kill curves showed that increasing concentrations did not result in progressively increased killing at concentrations >4 × MIC. Imipenem/XNW4107 has a low potential for resistance development in tested strains except for K. pneumoniae. Imipenem/XNW4107 provided good protection against imipenem-resistant A. baumannii and K. pneumoniae in vivo.

CONCLUSIONS:

The broad-spectrum profile and potent in vitro and in vivo antibacterial activities support imipenem/XNW4107 as a promising investigational candidate.

100 Deals associated with Funobactam

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute pyelonephritis	Phase 3	US	Evopoint Biosciences AU Pty Ltd	30 Mar 2023
Complicated urinary tract infection	Phase 3	US	Evopoint Biosciences AU Pty Ltd	30 Mar 2023
Pancreatitis	Phase 3	US	Evopoint Biosciences AU Pty Ltd	30 Mar 2023
Gram-Negative Bacterial Infections	Phase 3	US	Evopoint Biosciences Co., Ltd.Startup	06 Oct 2022
Gram-Negative Bacterial Infections	Phase 3	FR	Evopoint Biosciences Co., Ltd.Startup	06 Oct 2022
Gram-Negative Bacterial Infections	Phase 3	IL	Evopoint Biosciences Co., Ltd.Startup	06 Oct 2022
Gram-Negative Bacterial Infections	Phase 3	ES	Evopoint Biosciences Co., Ltd.Startup	06 Oct 2022
Hospital acquired bacterial pneumonia	Phase 3	US	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
Hospital acquired bacterial pneumonia	Phase 3	FR	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
Hospital acquired bacterial pneumonia	Phase 3	IL	Evopoint Biosciences AU Pty Ltd	31 Jul 2022