Delving into the Latest Updates on Recibokibart with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Recombinant humanized anti-interleukin 36R monoclonal antibody(Huaota Biopharma)

Target

IL-36R

Mechanism

IL-36R inhibitors(Interleukin-36 receptor inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal DiseasesOther Diseases+ [1]

Active Indication

Generalized Pustular PsoriasisColitis, UlcerativeSystemic Lupus Erythematosus

Inactive Indication-

Originator Organization

Huabo Biopharm Co Ltd.

Active Organization

Shanghai Huaaotai Biopharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 2/3

First Approval Date-

RegulationOrphan Drug (US)

Login to view timeline

Gene Sequence

Sequence Code 941453118H

Source: *****

Sequence Code 941453119L

Source: *****

AbstractCellular signaling via binding of the cytokines IL‐36α, β, and γ along with binding of the accessory protein IL‐36RAcP, to their cognate receptor IL‐36R is believed to play a major role in epithelial and immune cell‐mediated inflammation responses. Antagonizing the signaling cascade that results from these binding events via a directed monoclonal antibody provides an opportunity to suppress such immune responses. We report here the molecular structure of a complex between an extracellular portion of human IL‐36R and a Fab derived from a high affinity anti‐IL‐36R neutralizing monoclonal antibody at 2.3 Å resolution. This structure, the first of IL‐36R, reveals similarities with other structurally characterized IL‐1R family members and elucidates the molecular determinants leading to the high affinity binding of the monoclonal antibody. The structure of the complex reveals that the epitope recognized by the Fab is remote from both the putative ligand and accessory protein binding interfaces on IL‐36R, suggesting that the functional activity of the antibody is noncompetitive for these binding events.

01 Jan 2020·mAbsQ2 · MEDICINE

Preclinical characterization of the ADME properties of a surrogate anti-IL-36R monoclonal antibody antagonist in mouse serum and tissues

Q2 · MEDICINE

Article

Author: Soto, Marcus ; Thomas, Veena A. ; Pastuskovas, Cinthia V. ; Rock, Dan A. ; Conner, Kip P. ; Wagner, Mylo

The decision to pursue a monoclonal antibody (mAb) as a therapeutic for disease intervention requires the assessment of many factors, such as target-biology, including the total target burden and its accessibility at the intended site of action, as well as mAb-specific properties like binding affinity and the pharmacokinetics in serum and tissue. Interleukin-36 receptor (IL-36 R) is a member of the IL-1 family cytokine receptors and an attractive target to treat numerous epithelial-mediated inflammatory conditions, including psoriatic and rheumatoid arthritis, asthma, and chronic obstructive pulmonary disease. However, information concerning the expression profile of IL-36 R at the protein level is minimal, so the feasibility of developing a therapeutic mAb against this target is uncertain. Here, we present a characterization of the properties associated with absorption, distribution, metabolism, and excretion of a high-affinity IL-36 R-targeted surrogate rat (IgG2a) mAb antagonist in preclinical mouse models. The presence of IL-36 R in the periphery was confirmed unequivocally as the driver of non-linear pharmacokinetics in blood/serum, although a predominant site of tissue accumulation was not observed based upon the kinetics of radiotracer. Additionally, the contribution of IL-36 R-mediated catabolism of mAb in kidney was tested in a 5/6 nephrectomized mouse model where minimal effects on serum pharmacokinetics were observed, although analysis of functional mAb in urine suggests that target can influence the amount of mAb excreted. Our data highlight an interesting case of target-mediated drug disposition (TMDD) where low, yet broadly expressed levels of membrane-bound target result in a cumulative effect to drive TMDD behavior typical of a large, saturable target sink. The potential differences between our mouse model and IL-36 R target profile in humans are also presented.

04 Jul 2019·mAbsQ2 · MEDICINE

Retrospective analysis of model-based predictivity of human pharmacokinetics for anti-IL-36R monoclonal antibody MAB92 using a rat anti-mouse IL-36R monoclonal antibody and RNA expression data (FANTOM5)

Q2 · MEDICINE

Article

Author: Woska, Joseph R. ; Yang, Danlin ; Coble, Kelly ; Ruus, Peter ; Ahlberg, Jennifer ; Li, Hua ; Kroe-Barrett, Rachel ; Pamulapati, Chandrasena ; Brown, Su-Ellen ; Mbow, M. Lamine ; Giragossian, Craig ; Grimaldi, Christine ; Perez, Rocio ; Ganesan, Rajkumar ; Raymond, Ernie ; Caviness, Gary ; Myzithras, Maria ; Hansel, Steven ; Joseph, David

Accurate prediction of the human pharmacokinetics (PK) of a candidate monoclonal antibody from nonclinical data is critical to maximize the success of clinical trials. However, for monoclonal antibodies exhibiting nonlinear clearance due to target-mediated drug disposition, PK predictions are particularly challenging. That challenge is further compounded for molecules lacking cross-reactivity in a nonhuman primate, in which case a surrogate antibody selective for the target in rodent may be required. For these cases, prediction of human PK must account for any interspecies differences in binding kinetics, target expression, target turnover, and potentially epitope. We present here a model-based method for predicting the human PK of MAB92 (also known as BI 655130), a humanized IgG1 __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__κ monoclonal antibody directed against human IL-36R. Preclinical PK was generated in the mouse with a chimeric rat anti-mouse IgG2a surrogate antibody cross-reactive against mouse IL-36R. Target-specific parameters such as antibody binding affinity (K_D), internalization rate of the drug target complex (k_int), target degradation rate (k_deg), and target abundance (R₀) were integrated into the model. Two different methods of assigning human R₀ were evaluated: the first assumed comparable expression between human and mouse and the second used high-resolution mRNA transcriptome data (FANTOM5) as a surrogate for expression. Utilizing the mouse R₀ to predict human PK, AUC_0-∞ was substantially underpredicted for nonsaturating doses; however, after correcting for differences in RNA transcriptome between species, AUC_0-∞ was predicted largely within 1.5-fold of observations in first-in-human studies, demonstrating the validity of the modeling approach. Our results suggest that semi-mechanistic models incorporating RNA transcriptome data and target-specific parameters may improve the predictivity of first-in-human PK.

100 Deals associated with Recibokibart

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Generalized Pustular Psoriasis	Phase 3	CN	Shanghai Huaaotai Biopharmaceutical Co., Ltd.	02 Sep 2024
Colitis, Ulcerative	Phase 1	CN	Shanghai Huaaotai Biopharmaceutical Co., Ltd.	19 Aug 2022
Systemic Lupus Erythematosus	Phase 1	CN	Shanghai Huaaotai Biopharmaceutical Co., Ltd.	19 Aug 2022