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Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

Target

CD20 x Tubulin

Action

inhibitors

Mechanism

CD20 inhibitors(B-lymphocyte antigen CD20 inhibitors), Tubulin inhibitors

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

CD20 positive B-Cell Lymphoma

Inactive Indication

CD20 Positive B-Cell Non-Hodgkin LymphomaNon-Hodgkin's lymphoma refractory

Originator Organization

Shanghai Miracogen, Inc.

Active Organization

Shanghai Miracogen, Inc.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC39H67N5O7

InChIKeyDASWEROEPLKSEI-UIJRFTGLSA-N

CAS Registry474645-27-7

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This study consists of two parts. Phase Ia is a dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of MRG001. Phase Ib is a dose expansion study to assess the preliminary efficacy of MRG001 in patients with CD20-positive relapsed or refractory B-cell NHL at the confirmed RP2D. The safety, tolerability, pharmacokinetic (PK) and immunogenicity of MRG001 will be evaluated in both parts.

Start Date25 Jun 2019

Sponsor / Collaborator

Shanghai Miracogen, Inc.

100 Clinical Results associated with MRG-001

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100 Translational Medicine associated with MRG-001

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100 Patents (Medical) associated with MRG-001

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564

Literatures (Medical) associated with MRG-001

03 Feb 2025·Angewandte Chemie International Edition

Benzyl Ammonium Carbamates Undergo Two‐Step Linker Cleavage and Improve the Properties of Antibody Conjugates

Article

Author: Patel, Nimit L. ; Schnermann, Martin J. ; Kalen, Joseph ; Li, Xiaoyi

AbstractTargeted payload delivery strategies, such as antibody‐drug conjugates (ADCs), have emerged as important therapeutics. Although considerable efforts have been made in the areas of antibody engineering and labeling methodology, improving the overall physicochemical properties of the linker/payload combination remains an important challenge. Here we report an approach to create an intrinsically hydrophilic linker domain. We find that benzyl α‐ammonium carbamates (BACs) undergo tandem 1,6–1,2‐elimination to release secondary amines. Using a fluorogenic hemicyanine as a model payload component, we show that a zwitterionic BAC linker improves labeling efficiency and reduces antibody aggregation when compared to a commonly used para‐amino benzyl (PAB) linker as well as a cationic BAC. Cellular and in vivo fluorescence imaging studies demonstrate that the model payload is specifically released in antigen‐expressing cells and tumors. The therapeutic potential of the BAC linker strategy was assessed using an MMAE payload, a potent microtubule‐disrupting agent frequently used for ADC applications. The BAC‐MMAE combination enhances labeling efficiency and cellular toxicity when compared to the routinely used PAB‐Val‐Cit ADC analogue. Broadly, this strategy provides a general approach to mask payload hydrophobicity and improve the properties of targeted agents.

15 Jan 2025·Bioconjugate Chemistry

Delivery of Monomethyl Auristatin F to the Tumor Microenvironment with Noninternalizing Fibroblast Activation Protein-Cleavable Small Molecule–Drug Conjugates Elicits Potent In Vivo Anticancer Activity

Article

Author: Bocci, Matilde ; Principi, Lucrezia ; Neri, Dario ; Gilardoni, Ettore ; Cazzamalli, Samuele ; Galbiati, Andrea

OncoFAP is an ultrahigh affinity ligand of fibroblast activation protein (FAP), a tumor-associated antigen overexpressed in the stroma of the majority of solid tumors. OncoFAP has been previously implemented as a tumor-homing moiety for the development of small molecule drug conjugates (SMDCs). In the same context, the glycine--proline dipeptide was included with the aim to selectively undergo cleavage only in the presence of the target FAP, triggering the consequent release of the cytotoxic payload in the tumor microenvironment. In this work, we evaluate the use of monomethyl auristatin F (MMAF) as a payload, a close derivative of MMAE bearing a charged carboxylic acid that hampers its cellular permeability, typically employed in the development of internalizing antibody-drug conjugates. The novel OncoFAP-GlyPro-MMAF and the previously described OncoFAP-GlyPro-MMAE were compared in a head-to-head therapeutic experiment in mice bearing FAP-positive tumors. Surprisingly, the MMAF conjugate mediated potent antitumor activity, despite its poor cellular permeability.

31 Dec 2024·OncoImmunology

CD20 expression regulates CD37 levels in B-cell lymphoma – implications for immunotherapies

Article

Author: Inderberg, Else Marit ; Graczyk-Jarzynka, Agnieszka ; Granica, Monika ; Majchrzak, Martyna ; Domagala, Joanna ; Dostalova, Lenka ; Firczuk, Malgorzata ; Forcados, Christopher ; Marhelava, Katsiaryna ; Poreba, Marcin ; Barankiewicz, Joanna ; Zhylko, Andriy ; Gehlert, Carina Lynn ; Kusowska, Aleksandra ; Fidyt, Klaudyna ; Krawczyk, Marta ; Peipp, Matthias ; Bobrowicz, Malgorzata ; Szumera-Cieckiewicz, Anna ; Baranowska, Iwona ; Winiarska, Magdalena ; Šmída, Michal ; Wälchli, Sébastien ; Slusarczyk, Aleksander ; Prochorec-Sobieszek, Monika ; Pepek, Monika ; Kubacz, Matylda

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.

100 Deals associated with MRG-001

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
CD20 positive B-Cell Lymphoma	Phase 1	China	Shanghai Miracogen, Inc.	25 Jun 2019
CD20 Positive B-Cell Non-Hodgkin Lymphoma	Discovery	China	Shanghai Miracogen, Inc.	25 Jun 2019
Non-Hodgkin's lymphoma refractory	Discovery	China	Shanghai Miracogen, Inc.	25 Jun 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2023	Phase 1	Diffuse large B-cell lymphoma recurrent	35	MRG001 1.8 mg/kg	(dwxedybfkd) = ewzfmpwtin ctdyufdcfz (lcgdepglgp, 22.2 - 56.4) View more	-	10 Dec 2023

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Translational Medicine

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Deal

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Core Patent

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Clinical Trial

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Approval

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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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