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

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.