ArticleBlood2021
A factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- [Chinese guidelines on the treatment of hemophilia (2025)].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Guideline
- Denecimig (Mim8) prophylaxis over 52 weeks in adolescents and adults with hemophilia A: FRONTIER2 extension study.Research and practice in thrombosis and haemostasis · 2026Trial
- Denecimig (Mim8) prophylaxis in children with hemophilia A with or without factor VIII inhibitors.Research and practice in thrombosis and haemostasis · 2026Trial
- Prediction of antibody non-specificity using protein language models and biophysical parameters.mAbs · 2026Article
- Of mice and FVIIIa mimetics: new hemophilia A models for in vivo evaluation.Blood advances · 2026Article
- A crowded podium in hemophilia A: when a low annualized bleeding rate is no longer enough to tell the contenders apart.Research and practice in thrombosis and haemostasis · 2026Article
- Current perspectives on non-factor therapies for hemophilia.International journal of hematology · 2026Review
- Divergent molecular strategies of next-generation activated factor VIII mimetics: insights from a direct comparative analysis.Research and practice in thrombosis and haemostasis · 2026Article
- Mechanism of action and impact on thrombin generation of denecimig (Mim8), emicizumab, and zemocimig (NXT007): comparative analysis using sequence-identical analogs.Research and practice in thrombosis and haemostasis · 2026Article
- Non-factor Therapies in Hemophilia: Mechanisms, Clinical Evidence, Patient Management, and Future Perspectives.Advances in therapy · 2026Review
- HMB-002: a monovalent antibody that elevates circulating VWF and FVIII levels for treatment of von Willebrand disease.Blood advances · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Next-generation FVIIIa-mimetic bispecific antibody NXT007: evaluation in preclinical models of hemostasis and thrombosis.Blood advances · 2026Article
- Factor VIIIResearch and practice in thrombosis and haemostasis · 2026Article
- Mathematical analysis of emicizumab: affinity-driven complex formation and lipid-surface reactions.Journal of thrombosis and haemostasis : JTH · 2025Article
- ComparativeResearch and practice in thrombosis and haemostasis · 2025Article
- FRONTIER1 multiple ascending dose extension: a safety, tolerability, pharmacokinetics, and pharmacodynamics study of Mim8 in people with hemophilia A.Research and practice in thrombosis and haemostasis · 2025Article
- Estimating the Factor VIII-Equivalent Activity of Emicizumab Using Global Assays of Haemostasis.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Article
- Consistent clinical factor VIII equivalency is unlikely for non-factor therapies in hemophilic mice.Haematologica · 2025Article
- GPD2 inhibition impairs coagulation function via ROS/NF-κB/P2Y12 pathway.Cellular & molecular biology letters · 2025Article
Corrections and comments
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Authors and funding
32 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemophilia A is a bleeding disorder resulting from deficient factor VIII (FVIII), which normally functions as a cofactor to activated factor IX (FIXa) that facilitates activation of factor X (FX). To mimic this property in a bispecific antibody format, a screening was conducted to identify functional pairs of anti-FIXa and anti-FX antibodies, followed by optimization of functional and biophysical properties. The resulting bispecific antibody (Mim8) assembled efficiently with FIXa and FX on membranes, and supported activation with an apparent equilibrium dissociation constant of 16 nM. Binding affinity with FIXa and FX in solution was much lower, with equilibrium dissociation constant values for FIXa and FX of 2.3 and 1.5 µM, respectively. In addition, the activity of Mim8 was dependent on stimulatory activity contributed by the anti-FIXa arm, which enhanced the proteolytic activity of FIXa by 4 orders of magnitude. In hemophilia A plasma and whole blood, Mim8 normalized thrombin generation and clot formation, with potencies 13 and 18 times higher than a sequence-identical analogue of emicizumab. A similar potency difference was observed in a tail vein transection model in hemophilia A mice, whereas reduction of bleeding in a severe tail-clip model was observed only for Mim8. Furthermore, the pharmacokinetic parameters of Mim8 were investigated and a half-life of 14 days shown in cynomolgus monkeys. In conclusion, Mim8 is an activated FVIII mimetic with a potent and efficacious hemostatic effect based on preclinical data.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.