PB0509 - Phase 1a Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Single Ascending Doses of Intravenous TU7710 in Warfarin Pretreated Healthy Male Subjects

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Byungwook Kim, MD, Ph.D

Clinical Professor
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital
Seongnam-si, Kyonggi-do, Republic of Korea

Co-Author(s)

KY

Kyung-Sang Yu

Professor
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital
Seongnam-si, Kyonggi-do, Republic of Korea
Hj

Heeyeon jung

Clinical Development Manager
Tiumbio Co.,Ltd
seongnam-si, Kyonggi-do, Republic of Korea
ML

Minsun Lee

Head of Biotherapeutics team
Tiumbio Co.,Ltd
Sungnam, Kyonggi-do, Republic of Korea
IS

Inyoung Song

Director of Biopharmaceutics, Executive Vice President
Tiumbio Co.,Ltd
Seongnam-si, Kyonggi-do, Republic of Korea
SI

Sohee Im

ADME Department Team Leader
Tiumbio Co.,Ltd
Seongnam-si, Kyonggi-do, Republic of Korea
JN

Ji-hyun Noh

Pharmacology Department Manager
Tiumbio Co.,Ltd
Seongnam-si, Kyonggi-do, Republic of Korea
YP

Yoojin Park

Regulatory Affairs Manager
Tiumbio Co.,Ltd
Seongnam-si, Kyonggi-do, Republic of Korea
HS

Hyesung Shin

Clinical Development Director
Tiumbio Co.,Ltd
Seongnam-si, Kyonggi-do, Republic of Korea

Background: TU7710 is a novel recombinant fusion protein linking activated FVII with human transferrin (rVIIa-TF). In nonclinical studies, TU7710 exhibited hemostatic effects and a prolonged half-life. It is in development as an on-demand treatment for hemophilia patients with inhibitors.

Aims: TUB4PI-01 study (NCT06025552) is aimed to assess the pharmacokinetics (PK), pharmacodynamics (PD), and safety of single ascending doses of intravenous TU7710 in warfarin pretreated healthy male subjects.

Methods: In a double-blind, placebo-controlled, single ascending dose design, 5 dose-levels (100, 200, 400, 800 μg/kg, last dose to be determined) will be investigated, with 8 healthy subjects per cohort randomized to receive either TU7710 or placebo in 6:2 ratio. Prior to TU7710 treatment, subjects underwent 8-day warfarin pretreatment to achieve a steady-state INR level ranging from 2.00 to 3.00. A single IV dose of TU7710 or placebo was administered. Warfarin administration was continued for 4 days post administration. Plasma FVIIa activity (PK), INR (PD), and safety profiles were assessed. Anti-drug antibodies will be assessed. Informed consent and ethics committee approval were obtained.

Results: Cohort 1 (100 μg/kg) and Cohort 2 (200 μg/kg) have been completed, while Cohort 3 to 5 is currently ongoing. Following TU7710 dosing, a significant increase in plasma FVIIa activity was observed in 6 PK data from each Cohort. The average mean residence times (MRTs) were 6.15 and 7.47 hours; the median terminal half-life was 13.80 and 12.39 hours; and the mean maximum plasma FVIIa activity (Cmax) was 8.62 and 13.46 IU/mL for Cohort 1 and 2, respectively (Table 1). A marked decrease in INR was observed after TU7710 administration (Figure 1). All adverse events were of mild intensity.

Conclusion(s): TU7710 displayed prolonged half-life and successfully achieved normal INR level in healthy subjects pre-treated with warfarin. This data provides support for the potential application of TU7710 in the treatment of hemophilia patients with inhibitors.