Delving into the Latest Updates on ABBV-MALT1 with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

Mechanism

Bcl-2 inhibitors(Apoptosis regulator Bcl-2 inhibitors), MALT1 inhibitors(Mucosa-associated lymphoid tissue lymphoma translocation protein 1 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

B-Cell LymphomaLeukemia

Inactive Indication-

Originator Organization

AbbVie Biotherapeutics, Inc.

Active Organization

AbbVie Biotherapeutics, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Green, Michael R ; Meulbroek, Jonathan A ; Panchal, Sanjay C ; Judge, Russell A ; Jung, Paul ; Dowell, Colleen ; Plotnik, Joshua P ; Yang, Haopeng ; Rojas, Estela ; Wilson, Ashley ; George, Mariam D ; Bontcheva, Velitchka ; Jhala, Manisha ; Pan, Chin ; Zhu, Haizhong ; Kohlhapp, Frederick J ; Qiu, Wei ; McClure, Ryan A ; Partha, Sarathy Karunan ; Will, Christine ; Parsons, Sydney ; Richardson, Adam E ; Ramathal, Cyril Y ; Pappano, William N ; Mali, Raghuveer Singh ; Ravanmehr, Vida ; Henderson, Jared ; Mastracchio, Anthony ; Elsen, Nathaniel L

AbstractThe activated B cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic B-cell receptor signaling and associated with poor outcomes when treated with standard therapy. In ABC-DLBCL, MALT1 is a core enzyme that is constitutively activated by stimulation of the B-cell receptor or gain-of-function mutations in upstream components of the signaling pathway, making it an attractive therapeutic target. We discovered a novel small-molecule inhibitor, ABBV-MALT1, that potently shuts down B-cell signaling selectively in ABC-DLBCL preclinical models leading to potent cell growth and xenograft inhibition. We also identified a rational combination partner for ABBV-MALT1 in the BCL2 inhibitor, venetoclax, which when combined significantly synergizes to elicit deep and durable responses in preclinical models. This work highlights the potential of ABBV-MALT1 monotherapy and combination with venetoclax as effective treatment options for patients with ABC-DLBCL.

100 Deals associated with ABBV-MALT1

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