PB1516 - CT-001, a Novel Factor VIIa, Demonstrates Enhanced In Vitro Procoagulant Activity in Peripartum Patient Samples

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Derek S. Sim, PhD

Chief Scientific Officer
Coagulant Therapeutics
Berkeley, California, United States

Co-Author(s)

TH

Terry W. Hermiston

Chief Executive Officer
Coagulant Therapeutics
Berkeley, California, United States
TA

Terrence Allen

Associate Professor
Duke University
Durham, North Carolina, United States
DB

Daekyeong Bae

Senior Director
Coagulant Therapeutics
Seoul, Seoul-t'ukpyolsi, Republic of Korea
JG

Jennifer Gilner

Assistant Professor
Duke University
Durham, North Carolina, United States
SK

Seung-Chul Kim

Professor
Pusan National University Hospital
Busan, Pusan-jikhalsi, Republic of Korea
SL

Sul Lee

Professor
Pusan National University Hospital
Busan, Pusan-jikhalsi, Republic of Korea
CM

Cornell R. Mallari

Scientist
Coagulant Therapeutics
Berkeley, California, United States
Andra James, MD, MPH (she/her/hers)

Professor Emeritus of Obstetrics & Gynecology - Division of Maternal-Fetal Medicine
Duke University, Durham, NC, USA
Durham, North Carolina, United States

Background: Severe postpartum hemorrhage (sPPH) non-responsive to first-line procedures and uterotonics is treated with invasive second-line interventions to control blood loss. Recombinant Factor VIIa (rFVIIa) has demonstrated some efficacy but its use has been limited because of thromboembolic risks. CT-001 is a novel rFVIIa with 4 N-glycans (T106N/N145/V253N N322) lacking terminal sialic acid residues to promote active clearance via the asialoglycoprotein receptor for lower thrombogenicity risk, and P10Q/K32E substitutions in the gamma-carboxyglutamic (Gla)-domain for enhanced activity. CT-001 is being developed for sPPH with increased safety and activity to reduce invasive second-line interventions.

Aims: We sought to evaluate the peripartum hemostasis status of pregnant women and assess the ex vivo hemostatic activity of CT-001 in peripartum blood samples.

Methods: 28 pregnant women with informed consent from 2 study sites were enrolled in this Institution Review Board-approved prospective observational study. Women at higher risk of PPH were preferentially enrolled. Baseline blood samples were collected up to 3 days before delivery. Post-delivery samples were collected 45 (+/-15) mins after delivery.

Results: After delivery, a significant decrease in hemoglobin, hematocrit, tissue factor, factor VIII, factor V, factor X, fibrinogen and protein C as well as an increase in D-dimer were observed. These changes were mild and reflective of the biological process of delivery, and peripartum supportive treatment (Table 1). Both samples from before and after delivery responded to CT-001 and rFVIIa treatment with CT-001 showing 2- to 7- fold higher potency than rFVIIa in PT, APTT, thrombin generation assay (TGA), and viscoelastic hemostatic assay (VHA, Table 2).

Conclusion(s): The enhanced procoagulant activity of CT-001 observed in this study together with the previously reported rapid clearance and low thrombogenicity of CT-001 in pre-clinical studies suggest that CT-001 has the potential for being an efficacious therapy for sPPH with increased safety over rFVIIa.