OC 40.1 - FRONTIER1: A Phase 1/2 Dose Escalation Study of a Novel Factor VIIIa Mimetic Bispecific Antibody, Mim8, for Evaluation of Safety, Pharmacokinetics, and Efficacy

Monday, July 11, 2022

2:45 PM – 3:00 PM

Location: ExCel Center, ICC Auditorium

Presentation Format: In-Person

Presenting Author(s)

Pratima Chowdary, MD

Consultant Haematologist
Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, United Kingdom
London, England, United Kingdom

Co-Author(s)

Francisco José López Jaime, MD

Hematologist
Hemostasis and Thrombosis Unit, Regional University Hospital of Málaga, IBIMA, Málaga, Spain.
Málaga, Andalucia, Spain
Johnny Mahlangu, MD, MMed

Professor in Haematology
University of the Witwatersrand and NHLS
Johannesburg, South Africa
CE

Christian Winther Eskelund

International Medical Manager
Novo Nordisk A/S
Søborg, Hovedstaden, Denmark
RM

Rikke Medom Meldgaard

Professor
Novo Nordisk A/S
Søborg, Hovedstaden, Denmark
PP

Paula Persson

Clinical Pharmacology Specialist
Novo Nordisk A/S
Søborg, Hovedstaden, Denmark
Jerzy Windyga, MD, PhD

Professor
Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
Warsaw, Mazowieckie, Poland

Background: Mim8 is a subcutaneously administered novel factor IXa/X bispecific antibody in development for patients with haemophilia A (PwHA) with or without inhibitors, which has demonstrated an efficacious haemostatic effect in nonclinical studies.

Aims: FRONTIER1 (EudraCT:2019-000465-20; NCT04204408) aims to investigate safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of Mim8 in healthy participants; and multiple ascending doses of Mim8 in PwHA, with or without inhibitors. Additionally, the study aims to provide data for dose-setting in subsequent FRONTIER studies.

Methods: In the single ascending dose (SAD) phase, healthy subjects received single ascending doses of Mim8 (targeting plasma exposures of 0.05–3 µg/ml) or placebo. In the multiple ascending dose (MAD) phase, PwHA received multiple ascending doses of Mim8 targeting an average plasma exposure of 1 µg/ml (cohort 1, QW dosing), 3 µg/ml (cohort 2, QW dosing), or 9 µg/ml (cohort 3, QW dosing, and cohort 4, Q4W dosing). Informed consent and ethics committee approval were obtained.

Results: Mim8 was well tolerated following both single and multiple dosing, and no thromboembolic events or related serious adverse events were reported. No occurrences of anti-Mim8 antibodies were reported. The increases in AUC and Cmax with increasing dose were consistent with dose-proportionality (Figure 1). Data from the SAD section suggests that T1/2 was 30.4 days, and Tmax was 9.1 days.
During the 12-week observation period, 15 treated bleeds were reported in 8 patients, of which 13 bleeds (9 traumatic) were observed in 6 patients from the lowest dose cohort. The 2 bleeds in patients from cohorts 2 and 3 were traumatic, thus neither treated joint nor spontaneous bleeds were observed beyond cohort 1 (Table 1).

Conclusion(s): Pharmacokinetic properties were consistent with dose-proportionality and support weekly and monthly dosing approaches. Mim8 was well tolerated and no occurrences of anti-Mim8 antibodies were reported. FRONTIER1 provides encouraging data supporting further clinical development.