Delving into the Latest Updates on 1D8N/CEGa1 with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms-

Target

4-1BB x EGFR

Action

agonists, antagonists

Mechanism

4-1BB agonists(Tumor necrosis factor receptor superfamily member 9 agonists), EGFR antagonists(Epidermal growth factor receptor erbB1 antagonists)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

LeadArtis SL

Active Organization

LeadArtis SL

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Tapia-Galisteo, Antonio ; Martínez-Torrecuadrada, Jorge ; Lykkemark, Simon ; Harwood, Seandean Lykke ; Mikkelsen, Kasper ; Blanco, Francisco J ; Caleiras, Eduardo ; Cuesta, Angel M ; Navarro, Rocio ; Aznar, M Angela ; Melero, Ignacio ; Zapata, Juan M ; Alvarez-Vallina, Luis ; Compte, Marta ; Zonca, Manuela ; Erce-Llamazares, Ainhoa ; Nuñez-Prado, Natalia ; Bernardino de la Serna, Jorge ; Merino, Nekane ; Sanz, Laura ; Perez-Chacon, Gema ; Muñoz, Ines G

AbstractThe costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with FcγR interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8N/CEGa1, consisting of three anti-4-1BB single-chain variable fragments and three anti-EGFR single-domain antibodies positioned in an extended hexagonal conformation around the collagen XVIII homotrimerization domain. The1D8N/CEGa1 trimerbody demonstrated high-avidity binding to 4-1BB and EGFR and a potent in vitro costimulatory capacity in the presence of EGFR. The trimerbody rapidly accumulates in EGFR-positive tumors and exhibits anti-tumor activity similar to IgG-based 4-1BB-agonistic mAbs. Importantly, treatment with 1D8N/CEGa1 does not induce systemic inflammatory cytokine production or hepatotoxicity associated with IgG-based 4-1BB agonists. These results implicate FcγR interactions in the 4-1BB-agonist-associated immune abnormalities, and promote the use of the non-canonical antibody presented in this work for safe and effective costimulatory strategies in cancer immunotherapy.

100 Deals associated with 1D8N/CEGa1

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	-	LeadArtis SL	-

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Clinical Result

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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