Next-generation FVIIIa-mimetic bispecific antibody NXT007: evaluation in preclinical models of hemostasis and thrombosis Article Swipe
Matthew Locke
,
Nina Frey
,
Mukul Girotra
,
Mariella Wyssenbach
,
Lejla Bektic
,
Tovo David
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2025018215
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2025018215
NXT007 is a next-generation factor (F)VIIIa-mimetic bispecific antibody currently in Phase 1/2 trials. It was developed by optimizing the framework of emicizumab to achieve hemostatic normalization in people with hemophilia A (PwHA). Here, we provide a direct comparison of NXT007 with emicizumab, using a wide range of in vitro and in vivo preclinical models of hemostasis and thrombosis. NXT007 and emicizumab increased tissue factor (TF)-triggered peak height thrombin generation when spiked into HA-like (FVIII-neutralized) plasma, with NXT007 being more potent than emicizumab, peaking at lower concentrations and with higher maximum effect. NXT007 and emicizumab delayed fibrinolysis in a dose-dependent manner, with NXT007 having ~20-fold more potent antifibrinolytic effect. Both bispecific antibodies corrected clotting times and kinetics of HA-like blood, measured by rotational thromboelastometry, with NXT007 being ~23-fold more potent. In collagen/TF-coated flow chambers perfused with HA-like blood at arterial shear rates, NXT007 and emicizumab increased fibrin deposition without increasing platelet adherence; maximum effect of NXT007 was greater than emicizumab and achieved at lower concentration. Following tail vein transection in HA mice, NXT007 was more potent than emicizumab in controlling bleeding. In a ferric chloride carotid injury model, administration of NXT007 and emicizumab at plasma concentrations ~20-200µg/mL had no effect on maximum blood flow reduction, indicating that they do not present a prothrombotic profile in this model. Overall, our data support the ongoing clinical evaluation of NXT007 and suggest that it has potential to substantially improve therapeutic efficacy for PwHA.
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Metadata
- Type
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- Language
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- Landing Page
- https://doi.org/10.1182/bloodadvances.2025018215
- https://ashpublications.org/bloodadvances/article-pdf/doi/10.1182/bloodadvances.2025018215/2422632/bloodadvances.2025018215.pdf
- OA Status
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- https://openalex.org/W4416507870
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4416507870Canonical identifier for this work in OpenAlex
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https://doi.org/10.1182/bloodadvances.2025018215Digital Object Identifier
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Next-generation FVIIIa-mimetic bispecific antibody NXT007: evaluation in preclinical models of hemostasis and thrombosisWork title
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articleOpenAlex work type
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enPrimary language
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2025Year of publication
- Publication date
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2025-11-21Full publication date if available
- Authors
-
Matthew Locke, Nina Frey, Mukul Girotra, Mariella Wyssenbach, Lejla Bektic, Tovo DavidList of authors in order
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https://doi.org/10.1182/bloodadvances.2025018215Publisher landing page
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https://ashpublications.org/bloodadvances/article-pdf/doi/10.1182/bloodadvances.2025018215/2422632/bloodadvances.2025018215.pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://ashpublications.org/bloodadvances/article-pdf/doi/10.1182/bloodadvances.2025018215/2422632/bloodadvances.2025018215.pdfDirect OA link when available
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| abstract_inverted_index.substantially | 233 |
| abstract_inverted_index.~20-200µg/mL | 195 |
| abstract_inverted_index.(TF)-triggered | 64 |
| abstract_inverted_index.administration | 187 |
| abstract_inverted_index.concentration. | 163 |
| abstract_inverted_index.concentrations | 85, 194 |
| abstract_inverted_index.dose-dependent | 98 |
| abstract_inverted_index.next-generation | 3 |
| abstract_inverted_index.(F)VIIIa-mimetic | 5 |
| abstract_inverted_index.antifibrinolytic | 106 |
| abstract_inverted_index.collagen/TF-coated | 130 |
| abstract_inverted_index.(FVIII-neutralized) | 73 |
| abstract_inverted_index.thromboelastometry, | 122 |
| cited_by_percentile_year | |
| countries_distinct_count | 1 |
| institutions_distinct_count | 6 |
| citation_normalized_percentile |