OC 78.3 - HMB-001 – a novel bispecific antibody accumulating and targeting endogenous FVIIa to activated platelets for subcutaneous prophylaxis in multiple bleeding disorders including Glanzmann Thrombasthenia

Wednesday, July 13, 2022

10:45 AM – 11:00 AM

Location: ExCel Center, ICC Capital Suite Room 1

Presentation Format: In-Person

Presenting Author(s)

Henrik Ostergaard, PhD

Scientific Director
Hemab Therapeutics
Copenhagen, Hovedstaden, Denmark

Co-Author(s)

Minka Zivkovic, MSc

Ph.D. candidate
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Utrecht, Utrecht, Netherlands
PG

Prafull S. Gandhi

Scientific Director
Hemab Therapeutics
Copenhagen, Hovedstaden, Denmark
MK

Mads Kjelgaard-Hansen

Principal Scientist
Novo Nordisk
Copenhagen, Hovedstaden, Denmark
MB

Mie L. Broberg

Pharmacokineticist
Novo Nordisk
Copenhagen, Hovedstaden, Denmark
TE

Torben Elm

Senior Scientist
Novo Nordisk
Copenhagen, Hovedstaden, Denmark
MS

Mette Stougaard Kyhn

Senior Scientist
Novo Nordisk
Copenhagen, Hovedstaden, Denmark
ML

Monika N. Løvgreen

Coordinator
Novo Nordisk
Copenhagen, Hovedstaden, Denmark
EO

Eva H. Olsen

Director
Hemab Therapeutics
Copenhagen, Hovedstaden, Denmark
CR

Catherine J. Rea

Medical Director
Hemab Therapeutics
41 King George Square, Richmond, England, United Kingdom
BS

Benny Sorensen

CEO
Hemab Therapeutics
Cambridge, Massachusetts, United States
SB

Soren E. Bjorn

Co-founder
Hemab Therapeutics
Copenhagen, Hovedstaden, Denmark
Roger E.G. Schutgens, MD, PhD, MSc

Internist-hematologist, Professor
Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht and University Utrecht, Utrecht, The Netherlands
Utrecht, Utrecht, Netherlands
RU

Rolf T. Urbanus

Associate Professor
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Utrecht, Utrecht, Netherlands
JF

Johan H. Faber

Co-founder & CTO
Hemab Therapeutics
Copenhagen, Hovedstaden, Denmark

Background: HMB-001 is a bispecific antibody that binds and accumulates endogenous FVIIa in circulation. Upon vessel injury, HMB-001 promotes local FX activation and thrombin generation by placing FVIIa on the surface of activated platelets via binding to the TREM-like transcript 1 (TLT-1) receptor. The activity of HMB-001 thus builds on the mechanism of action (MoA) of recombinant FVIIa (rFVIIa) and has the potential to prevent bleeds in multiple hemostatic disorders of which Glanzmann Thrombasthenia (GT) is the primary focus. GT is characterized by defective platelet aggregation and frequent bleeding episodes. With no available prophylactic treatment in GT, HMB-001 could address a significant unmet need.

Aims: Investigate the therapeutic potential of HMB-001 in GT and hemophilia A (HA).

Methods: A PK/PD study was performed in cynomolgus monkey with antibody and FVIIa quantification using ELISA and activity assays, respectively. The activity of HMB-001 was studied by thromboelastography in human HA (FVIII-depleted) whole blood and in a platelet aggregation assay with GT platelets. The effect rFVIIa +/- HMB-001 on bleeding was determined in the tail vein transection (TVT) model in HA mice.

Results: Multiple-dose subcutaneous administration of HMB-001 in cynomolgus monkeys resulted in the accumulation of endogenous FVIIa to low nM levels. Upon supplementation of corresponding levels of rFVIIa to ex vivo models of GT and HA, HMB-001 was shown to potentiate the activity of FVIIa by 6-14 fold in a TLT-1 dependent manner reaching activity levels in the therapeutic range by comparison to rFVIIa. A similar enhancement of the hemostatic activity of FVIIa by HMB-001 was demonstrated in the mouse TVT injury model upon co-administration of rFVIIa and HMB-001.

Conclusion(s): Combining ex vivo and animal models, the present study supports that HMB-001 can enhance the activity of endogenous FVIIa to levels that are considered therapeutically effective in GT and HA based on clinical experience with rFVIIa.