Delving into the Latest Updates on Imalumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-MIF monoclonal antibody, Immunoglobulin g1-kappa, anti-(homo sapiens mif (macrophage migration inhibitory factor, glycosylation-inhibiting factor, glif, gif)), homo sapiens monoclonal antibody

+ [1]

Target

MIF

Mechanism

MIF inhibitors(Macrophage migration inhibitory factor inhibitors), Immunomodulators

Therapeutic Areas

NeoplasmsDigestive System DisordersOther Diseases

Active Indication

AscitesColorectal Cancer

Inactive Indication

Lupus NephritisMalignant ascitesMetastatic Colorectal Carcinoma+ [2]

Originator Organization

Cytokine PharmaSciences, Inc.

Active Organization

Cytokine PharmaSciences, Inc.

Baxalta, Inc.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 9057749L

Source: *****

Sequence Code 9057845H

Source: *****

A Phase 1/2a, Open-Label, Parallel, Two-Arm, Dose-EscalationStudy to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of BAX69 in Subjects with Refractory Ovarian Cancer with Malignant Ascites - Phase 1/2a Two-Arm, Dose-Escalation of BAX69 in subjects with Malignant Ascites of Ovarian Cancer

Start Date02 Mar 2016

Sponsor / Collaborator

Baxalta Innovations GmbH

NCT02540356

/ TerminatedPhase 1/2

A Phase 1/2a, Open-Label, Parallel, Two-Arm Dose-Escalation Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of BAX69 in Subjects With Refractory Ovarian Cancer With Malignant Ascites

The purpose of this study is to evaluate the safety and tolerability of BAX69 monotherapy given either as intraperitoneal (IP) infusion (Single-Route Arm); or as IP infusion after intravenous (IV) infusion (IV+IP) (Double-Route Arm), and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for each Arm separately, in subjects with refractory ovarian cancer and recurrent malignant ascites. In both Arms, the plasma pharmacokinetics (PK) of BAX69 will be characterized, and pharmacodynamics (PD) markers will be explored in plasma and ascites. Two expansion cohorts will further assess the tolerability of the RP2D and explore clinical signs of efficacy.

Start Date02 Nov 2015

Sponsor / Collaborator

Baxalta, Inc.

NCT02448810

/ TerminatedPhase 2

A Phase 2a Randomized, Open-label Study to Assess the Safety, Tolerability, and Efficacy of BAX69 in Combination With 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer

The purpose of this study is to evaluate the safety and tolerability of BAX69 in combination with 5-fluorouracil (5-FU)/leucovorin (LV) or panitumumab to determine the recommended phase II dose (RP2D) of each combination; and to compare the efficacy between BAX69 in combination with 5-FU/LV for subjects with KRAS or NRAS mutated tumor (mt) or panitumumab, for subjects with KRAS and NRAS wild type tumor (wt) and standard of care (SoC) per investigator choice as third or fourth treatment line in subjects with progressive measurable metastatic colorectal cancer (mCRC).

Start Date15 Jun 2015

Sponsor / Collaborator

Baxalta, Inc.

100 Clinical Results associated with Imalumab

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100 Translational Medicine associated with Imalumab

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100 Patents (Medical) associated with Imalumab

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92

Literatures (Medical) associated with Imalumab

01 Jan 2025·Translational Oncology

Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells

Article

Author: Zhou, Qi ; Yue, Zhen-Qi ; Fan, Luo-Jun ; Xu, He-Song ; Yue, Zhen- Qi ; Xin, Lin ; Liu, Jiang ; Zou, Yong-Hui ; Lai, Jun-Yan ; Gan, Jin-Heng

BACKGROUNDThe limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/PD-1 blockades in gastric cancer.METHODSTo conduct MR, gastric carcinoma cells were transfected with LV-METase in vitro, and 615 mice were injected with MFC cells with stable METase expression in vivo. Flow cytometry was conducted to measure the proportions of M1/M2 macrophages and CD8⁺ GZMB⁺/IFN-γ⁺ T cells. Additionally, the levels of M1/M2 macrophage markers and MIF were also detected.RESULTSMR increased M1 and down-regulated M2 macrophages. MR suppressed MIF levels in gastric carcinoma cells, while the addition of anti-MIF neutralizing antibody inhibited the effect of MR on macrophage M1/M2 polarization. MR enhanced the increase of the proportion of CD8⁺ GZMB⁺ T cells and CD8⁺ IFN-γ⁺ T cells induced by PD-L1/PD-1 blockades. In vivo detection verified the efficacy of the combination of MR and PD-L1/PD-1 blockades on gastric cancer.CONCLUSIONSMR inhibits the secretion of MIF by gastric carcinoma cells, promotes macrophage M1 polarization, and enhances the therapeutic effect of PD-L1/PD-1 blockades in gastric cancer.

04 May 2023·Molecular cancer therapeutics

Preclinical Evaluation of ON203, A Novel Bioengineered mAb Targeting Oxidized Macrophage Migration Inhibitory Factor as an Anticancer Therapeutic.

Article

Author: Mirkina, Irina ; Kerschbaumer, Randolf J ; Maurer, Barbara ; Rossmueller, Gregor ; Mayer, Julia ; Hoeld, Verena ; Schinagl, Alexander ; Thiele, Michael

High levels of macrophage migration inhibitory factor (MIF) in patients with cancer are associated with poor prognosis. Its redox-dependent conformational isoform, termed oxidized MIF (oxMIF), is a promising tumor target due to its selective occurrence in tumor lesions and at inflammatory sites. A first-generation anti-oxMIF mAb, imalumab, was investigated in clinical trials in patients with advanced solid tumors, where it was well tolerated and showed signs of efficacy. However, imalumab has a short half-life in humans, increased aggregation propensity, and an unfavorable pharmacokinetic profile. Here, we aimed to optimize imalumab by improving its physicochemical characteristics and boosting its effector functions. Point mutations introduced into the variable regions reduced hydrophobicity and the antibodies' aggregation potential, and increased plasma half-life and tumor accumulation in vivo, while retaining affinity and specificity to oxMIF. The introduction of mutations into the Fc region known to increase antibody-dependent cellular cytotoxicity resulted in enhanced effector functions of the novel antibodies in vitro, whereas reduced cytokine release from human peripheral blood mononuclear cells in the absence of target antigen by the engineered anti-oxMIF mAb ON203 versus imalumab reveals a favorable in vitro safety profile. In vivo, ON203 mAb demonstrated superior efficacy over imalumab in both prophylactic and established prostate cancer (PC3) mouse xenograft models. In summary, our data highlight the potential of the second-generation anti-oxMIF mAb ON203 as a promising immunotherapy for patients with solid tumors, warranting clinical evaluation.

01 Dec 2021·Journal of Clinical InvestigationQ1 · MEDICINE

MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model

Q1 · MEDICINE

Article

Author: Pantouris, Georgios ; Fingerle-Rowson, Günter ; Holowka, Thomas ; Tilstam, Pathricia Veronica ; Schulte, Wibke ; Sauler, Maor ; Nouws, Jessica ; Bucala, Richard ; Leng, Lin ; Bernhagen, Jürgen ; Lolis, Elias ; Piecychna, Marta ; Kim, Bong-Sung

Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms predict mortality in different infections, and anti-MIF antibody improves survival in experimental models when administered 8 hours after infectious insult. The recent description of a second MIF superfamily member, D-dopachrome tautomerase (D-DT/MIF-2), prompted closer investigation of MIF-dependent responses. We subjected Mif-/- and Mif-2-/- mice to polymicrobial sepsis and observed a survival benefit with Mif but not Mif-2 deficiency. Survival was associated with reduced numbers of small peritoneal macrophages (SPMs) that, in contrast to large peritoneal macrophages (LPMs), were recruited into the peritoneal cavity. LPMs produced higher quantities of MIF than SPMs, but SPMs expressed higher levels of inflammatory cytokines and the MIF receptors CD74 and CXCR2. Adoptive transfer of WT SPMs into Mif-/- hosts reduced the protective effect of Mif deficiency in polymicrobial sepsis. Notably, MIF-2 lacks the pseudo-(E)LR motif present in MIF that mediates CXCR2 engagement and SPM migration, supporting a specific role for MIF in the recruitment and accumulation of inflammatory SPMs.

100 Deals associated with Imalumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Imalumab	-	DB15558

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ascites	Phase 2	-	Cytokine PharmaSciences, Inc.	-
Ascites	Phase 2	-	Baxalta, Inc.	-
Colorectal Cancer	Phase 2	-	Cytokine PharmaSciences, Inc.	-
Malignant ascites	Preclinical	US	Baxalta, Inc.	02 Nov 2015
Ovarian Cancer	Preclinical	US	Baxalta, Inc.	02 Nov 2015
Refractory Ovarian Carcinoma	Preclinical	US	Baxalta, Inc.	02 Nov 2015
Metastatic Colorectal Carcinoma	Preclinical	US	Baxalta, Inc.	15 Jun 2015
Lupus Nephritis	Preclinical	-	Cytokine PharmaSciences, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02540356 (CTgov)	Phase 1/2	Refractory Ovarian Carcinoma \| Malignant ascites	2	BAX69 Single-Route Arm (Single-Route Arm)	wxbpthmwyi(rfxslqsupb) = glthyfltty angekbcpcw (ddqxkqdksy, aoopqmttci - oglgoapwob) View more	-	15 Jun 2017
				BAX69 Double-Route Arm (Double-Route Arm)	wxbpthmwyi(rfxslqsupb) = vaqlqynqvw angekbcpcw (ddqxkqdksy, mdjexjmvit - whxyusccin) View more