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. 2023 Aug 23;7(6):102181.
doi: 10.1016/j.rpth.2023.102181. eCollection 2023 Aug.

Mim8, a novel factor VIIIa mimetic bispecific antibody, shows favorable safety and pharmacokinetics in healthy adults

Paula Persson  1 , Anne-Beth Amstrup  1 , Hans Veit Coester  2 , Irina Matytsina  1 , Selcuk Bas  3
Affiliations

Mim8, a novel factor VIIIa mimetic bispecific antibody, shows favorable safety and pharmacokinetics in healthy adults

Paula Persson et al. Res Pract Thromb Haemost. .

Abstract

Background: Mim8 (denecimig) is a novel activated coagulation factor VIII-mimetic bispecific antibody that assembles with activated coagulation FIX and FX on the platelet membrane surface.

Objectives: The FRONTIER1 (NCT04204408, NN7769-4513) single ascending dose and the 4882 pharmacokinetic (PK) studies (NCT05127473, NN7769-4882) examined the safety, tolerability, PK, and pharmacodynamics (PD) of Mim8 in healthy adult males.

Methods: The FRONTIER1 single ascending dose study consisted of 6 cohorts, each with 6 participants who received a single subcutaneous (s.c.) dose of Mim8 and 2 participants who received a placebo. The 4882 PK study had 11 arms, each with 6 participants who received a single s.c. dose of Mim8. The primary endpoint for both studies was treatment-emergent adverse events. Other safety assessments included relative changes in D-dimer, prothrombin fragments 1 and 2, fibrinogen, and platelets. The PK and PD were assessed using Mim8 plasma concentration and activated partial thromboplastin clotting time and thrombin generation, respectively.

Results: Mim8 was well tolerated, and there were no severe treatment-emergent adverse events. The PK properties of Mim8 in both studies were consistent with dose-proportionality. The terminal half-life of Mim8 after a single dose was approximately 1 month, and maximum plasma concentration was reached after 10 days.

Conclusion: The PK and PD profiles suggest that Mim8 is suitable as a long-acting FVIIIa-mimetic bispecific antibody for hemophilia A prophylaxis.

Keywords: factor VIII; hemophilia A; pharmacokinetics; safety; thrombin.

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Figures

None
Graphical abstract
Figure
Figure
Mean profiles of Mim8 plasma concentration (linear scale) - full analysis set. (A) FRONTIER1 SAD. (B) 4882 pharmacokinetic study. Mean ± standard error of the mean. Dotted horizontal line is a reference for lower limit of quantification.
See this image and copyright information in PMC

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