Delving into the Latest Updates on Dimeric glycoprotein VIFc(Corimmun) with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

Dimeric glycoprotein VI-Fc, GPVI-Fc, Revacept

+ [1]

Target

GPVI

Mechanism

GPVI inhibitors(Platelet membrane glycoprotein VI inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Acute Coronary SyndromeCoronary Artery Disease

Inactive Indication

Amaurosis FugaxAtherosclerosisCarotid Stenosis+ [4]

Originator Organization

Corimmun GmbH

Active Organization

Corimmun GmbH

Inactive Organization

advanceCOR GmbH

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks (TIAs), amaurosis fugax or stroke receive either Revacept (single dose) plus antiplatelet monotherapy or monotherapy alone.
Patients receive a single dose of trial medication by intravenous infusion for 20 minutes. Patients are followed up one and three days after treatment, at 3 months and by a telephone interview at 12 months.

Start Date08 Mar 2013

Sponsor / Collaborator

advanceCOR GmbH

100 Clinical Results associated with Dimeric glycoprotein VIFc(Corimmun)

Login to view more data

100 Translational Medicine associated with Dimeric glycoprotein VIFc(Corimmun)

Login to view more data

100 Patents (Medical) associated with Dimeric glycoprotein VIFc(Corimmun)

Login to view more data

34

Literatures (Medical) associated with Dimeric glycoprotein VIFc(Corimmun)

01 Jun 2023·Journal of Nuclear Medicine

Radiolabeled GPVI-Fc for PET Imaging of Multiple Extracellular Matrix Fibers: A New Look into Pulmonary Fibrosis Progression

Article

Author: Pichler, Bernd J ; Maurer, Andreas ; Gawaz, Meinrad ; Quintanilla-Martinez, Leticia ; Schaller, Martin ; Beziere, Nicolas ; Gonzalez-Menendez, Irene ; Isser, Simon ; Reischl, Gerald

Invariably fatal and with a particularly fast progression, pulmonary fibrosis (PF) is currently devoid of curative treatment options. Routine clinical diagnosis relies on breathing tests and visualizing the changes in lung structure by CT, but anatomic information is often not sufficient to identify early signs of progressive PF. For more efficient diagnosis, additional imaging techniques were investigated in combination with CT, such as ¹⁸F-FDG PET, although with limited success because of lack of disease specificity. Therefore, novel molecular targets enabling specific diagnosis are investigated, in particular for molecular imaging techniques. Methods: In this study, we used a ⁶⁴Cu-radiolabeled platelet glycoprotein VI fusion protein (⁶⁴Cu-GPVI-Fc) targeting extracellular matrix (ECM) fibers as a PET tracer to observe longitudinal ECM remodeling in a bleomycin-induced PF mouse model. Results: ⁶⁴Cu-GPVI-Fc showed significant uptake in fibrotic lungs, matching histology results. Contrary to ¹⁸F-FDG PET measurements, ⁶⁴Cu-GPVI-Fc uptake was linked entirely to the fibrotic activity of tissue and not was susceptible to inflammation. Conclusion: Our study highlights ⁶⁴Cu-GPVI-Fc as a specific tracer for ECM remodeling in PF, with clear therapy-monitoring and clinical translation potential.

01 Jun 2023·Thrombosis and Haemostasis

Pharmacological Inhibition of Glycoprotein VI- and Integrin α2β1-Induced Thrombus Formation Modulated by the Collagen Type

Article

Author: Heemskerk, Johan W. M. ; Farndale, Richard W. ; Watson, Steve P. ; Henskens, Yvonne M.C. ; Gawaz, Meinrad P. ; Jooss, Natalie J. ; Jandrot-Perrus, Martine ; Poulter, Natalie S.

Background In secondary cardiovascular disease prevention, treatments blocking platelet-derived secondary mediators pose a risk of bleeding. Pharmacological interference of the interaction of platelets with exposed vascular collagens is an attractive alternative, with clinical trials ongoing. Antagonists of the collagen receptors, glycoprotein VI (GPVI), and integrin α2β1, include recombinant GPVI-Fc dimer construct Revacept, 9O12 mAb based on the GPVI-blocking reagent Glenzocimab, Syk tyrosine-kinase inhibitor PRT-060318, and anti-α2β1 mAb 6F1. No direct comparison has been made of the antithrombic potential of these drugs. Methods Using a multiparameter whole-blood microfluidic assay, we compared the effects of Revacept, 9O12-Fab, PRT-060318, or 6F1 mAb intervention with vascular collagens and collagen-related substrates with varying dependencies on GPVI and α2β1. To inform on Revacept binding to collagen, we used fluorescent-labelled anti-GPVI nanobody-28. Results and Conclusion In this first comparison of four inhibitors of platelet–collagen interactions with antithrombotic potential, we find that at arterial shear rate: (1) the thrombus-inhibiting effect of Revacept was restricted to highly GPVI-activating surfaces; (2) 9O12-Fab consistently but partly inhibited thrombus size on all surfaces; (3) effects of GPVI-directed interventions were surpassed by Syk inhibition; and (4) α2β1-directed intervention with 6F1 mAb was strongest for collagens where Revacept and 9O12-Fab were limitedly effective. Our data hence reveal a distinct pharmacological profile for GPVI-binding competition (Revacept), GPVI receptor blockage (9O12-Fab), GPVI signaling (PRT-060318), and α2β1 blockage (6F1 mAb) in flow-dependent thrombus formation, depending on the platelet-activating potential of the collagen substrate. This work thus points to additive antithrombotic action mechanisms of the investigated drugs.

01 Feb 2023·Biophysical Journal

Investigating thrombin-loaded fibrin in whole blood clot microfluidic assay via fluorogenic peptide

Article

Author: Crossen, Jennifer ; Diamond, Scott L ; Shankar, Kaushik N

During clotting under flow, thrombin rapidly generates fibrin, whereas fibrin potently sequesters thrombin. This co-regulation was studied using microfluidic whole blood clotting on collagen/tissue factor, followed by buffer wash, and a start/stop cycling flow assay using the thrombin fluorogenic substrate, Boc-Val-Pro-Arg-AMC. After 3 min of clotting (100 s^-1) and 5 min of buffer wash, non-elutable thrombin activity was easily detected during cycles of flow cessation. Non-elutable thrombin was similarly detected in plasma clots or arterial whole blood clots (1000 s^-1). This thrombin activity was ablated by Phe-Pro-Arg-chloromethylketone (PPACK), apixaban, or Gly-Pro-Arg-Pro to inhibit fibrin. Reaction-diffusion simulations predicted 108 nM thrombin within the clot. Heparin addition to the start/stop assay had little effect on fibrin-bound thrombin, whereas addition of heparin-antithrombin (AT) required over 6 min to inhibit the thrombin, indicating a substantial diffusion limitation. In contrast, heparin-AT rapidly inhibited thrombin within microfluidic plasma clots, indicating marked differences in fibrin structure and functionality between plasma clots and whole blood clots. Addition of GPVI-Fab to blood before venous or arterial clotting (200 or 1000 s^-1) markedly reduced fibrin-bound thrombin, whereas GPVI-Fab addition after 90 s of clotting had no effect. Perfusion of AF647-fibrinogen over washed fluorescein isothiocyanate (FITC)-fibrin clots resulted in an intense red layer around, but not within, the original FITC-fibrin. Similarly, introduction of plasma/AF647-fibrinogen generated substantial red fibrin masses that did not penetrate the original green clots, demonstrating that fibrin cannot be re-clotted with fibrinogen. Overall, thrombin within fibrin is non-elutable, easily accessed by peptides, slowly accessed by average-sized proteins (heparin/AT), and not accessible to fresh fibrinogen.

100 Deals associated with Dimeric glycoprotein VIFc(Corimmun)

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
Atherosclerosis	Phase 2	GB	advanceCOR GmbH	08 Mar 2013
Atherosclerosis	Phase 2	DE	advanceCOR GmbH	08 Mar 2013
Carotid Stenosis	Phase 2	GB	advanceCOR GmbH	08 Mar 2013
Carotid Stenosis	Phase 2	DE	advanceCOR GmbH	08 Mar 2013
Ischemic Attack, Transient	Phase 2	GB	advanceCOR GmbH	08 Mar 2013
Ischemic Attack, Transient	Phase 2	DE	advanceCOR GmbH	08 Mar 2013
Stroke	Phase 2	GB	advanceCOR GmbH	08 Mar 2013
Stroke	Phase 2	DE	advanceCOR GmbH	08 Mar 2013
Acute Coronary Syndrome	Phase 2	-	Corimmun GmbH	-
Coronary Artery Disease	Phase 2	-	Corimmun GmbH	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01645306 (Pubmed)	Phase 2	Carotid Stenosis	160	Placebo	upqljmfiow(adfqnkjfnj) = noovgycrfo ptdapuaaix (gtfdtaamyw, 0.88 - 1.53)	Positive	13 Jun 2022
				Revacept 40 mg	upqljmfiow(adfqnkjfnj) = uutoskwaga ptdapuaaix (gtfdtaamyw, 0.78 - 1.42)