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On October 17, Gilead and MacroGenics announced an oncology collaboration, with Gilead obtaining exclusive licensing of the CD123×CD3 bispecific antibody MGD024, with the possibility of collaborating
on two other early-stage research projects.
Under the agreement, Gilead will pay an upfront payment of $60 million to MacroGenics, which will be eligible for target nominations, premiums, and development, regulatory and commercial milestones
of up to $1.
7 billion.
7 billion
MGD024
MGD024 MGD024 is a second-generation CD123 x CD3 DART molecule developed through MacroGenics' DART® platform and is designed to extend half-life and reduce cytokine release, making it suitable for intermittent dosing
.
Its main indication is acute myeloid leukemia (AML).
It is currently in phase I clinical trials
.
.
The first generation of Flotetuzumab (left) and the second generation of MGD024 (right) structure
In vitro studies, CD123 x CD3-V2 DART variants mediated depletion
of acute myeloid leukemia cells in vitro.
of acute myeloid leukemia cells in vitro.
In vivo studies, the CD123 x CD3-V2 DART variant demonstrated antitumor activity
in a mouse model reconstructed by human PBMC.
in a mouse model reconstructed by human PBMC.
DART Technology Platform The DART Technology Platform is a bispecific antibody construction technology jointly developed by MacroGenics and Servier, which can solve the problems of
bispecific antibody instability, short half-life and low synthesis efficiency.
Structurally, the bispecific antibody molecule developed based on this platform is a heterodimer antibody formed by the binding of two polypeptide chains:
Each peptide contains a VL domain, a short linker, a VH domain, a second linker including cysteine and a heterodimer domain, and cysteine residues covalently link the two peptide chains to form interchain disulfide bonds to improve structural stability.
At the same time, adding FC fragments to the basic DART molecule can increase the half-life from hours to days and weeks;
At the same time, adding FC fragments to the basic DART molecule can increase the half-life from hours to days and weeks; DART antibodies can accommodate virtually any variable region sequence and have predictable expression, folding, and antigen recognition
.
.
A: Basic DART molecular structure; B: Divalent DART molecule containing Fc; C: Tetravalent DART molecule containing Fc[1]
Gilead AML pipeline layout
Gilead AML pipeline layout Currently, Gilead's AML pipeline includes CD47 monoclonal antibody magrolimab and cell therapy KITE-222 (CLL-1).
KITE-222 is currently in clinical phase I, which was derived from Gilead's $11.
9 billion acquisition of Kite Pharma in 2017
.
In 2020, Gilead's Kite division signed a two-year research collaboration and licensing agreement
with Takingrade Biologics for acute myeloid leukemia (AML).
Highgrade will use its proprietary technology platform to identify new targets and anti-AML-specific antibodies for AML for use by Kite in cell therapy
.
The CD47 monoclonal antibody magrolimab is in clinical phase III, after the combination study of magrolimab + azacitidine was partially suspended by the FDA due to a significant imbalance
in suspected unexpected serious side effects reported by investigators in different experimental groups.
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