Coagulant Therapeutics Announces Publication of In Vivo Data Demonstrating Safety and Efficacy of CT-001 for the Management of Acute Bleeding

From the press release

Coagulant Therapeutics Corporation, a privately held company focused on the design, development and commercialization of therapeutics targeted to the coagulation cascade and its adjacencies, today announced results from in vivo studies for its lead product candidate, CT-001, published in the July 2022 edition of the journal, Thrombosis Research.

The manuscript, entitled “CT-001 Is a Rapid Clearing Factor VIIa with Enhanced Clearance and Hemostatic Activity for the Treatment of Acute Bleeding in Non-Hemophilia Settings,” showed that CT-001 is a safe and effective treatment of acute bleeding. CT-001 is a next-generation Factor VIIa (FVIIa)-based therapy, a recombinant and activated version of the coagulation factor, Factor VII, that is naturally found in the body and plays a key role in the arrest of bleeding. CT-001 has been engineered to limit its circulating half-life to only three (3) minutes in comparison to a half-life of two (2) hours for wild type (WT) FVIIa. This acceleration in clearance time from the body leads to improved safety in thrombogenicity models. In addition, CT-001 has been designed to have enhanced affinity to the cell surface which leads to an increase in activity. This results in superior efficacy in an acute bleeding model over recombinant FVIIa.

“Uncontrolled bleeding is the single largest cause of death among individuals ages 1 to 44 years. CT-001 has the potential to become the new standard of care to treat acute bleeding,”¹ said Terry Hermiston, Ph.D., founder and CEO of Coagulant Therapeutics. “We believe up to 40 percent of hemorrhage-related deaths could be prevented with the type of rapid hemostatic control demonstrated by CT-001.”^2,3

Engineering an improved FVII molecule: Characterization and in vivo validation

The in vivo studies compared the safety and efficacy of CT-001 versus recombinant FVIIa in multiple mouse models. The studies confirmed that desialylation of the molecule increased the speed by which it cleared from the body. The resultant shortened half-life translated to reduced pathologic thrombogenicity by comparison with the conventional recombinant FVIIa in two thrombosis models. These studies also tested the efficacy of the CT-001 molecule, engineered in the Gla domain (gamma-carboxyglutamic acid, a FVII amino acid sequence responsible for binding to the site of injury) for enhanced targeting and potency to compensate for the rapid clearance. In a mouse model of acute bleeding, CT-001 prevented mice from progressing to severe hemorrhage even with the increased clearance and demonstrated superiority to the native FVIIa molecule. The in vivo studies also confirmed the results of a 2021 study of CT-001 in in vitro systems published in the journal Research and Practice in Thrombosis and Haemostasis, which demonstrated the rapid clearance and enhanced potency of CT-001 versus recombinant FVIIa.[4]

“We feel that these studies support the potential utility of CT-001 in acute bleeding settings where there currently exists no approved pharmaceutical therapies. We are preparing for a Phase 1 clinical trial in the initial indication of severe postpartum hemorrhage, an indication of significant unmet medical need where we were recently granted orphan drug designation” stated Hermiston.

About CT-001

CT-001 is an engineered version of FVIIa that is designed to address the limitations of the recombinant FVIIa, approved for use in Hemophilia A and B patients with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions but not approved for use in the acute bleeding settings such as trauma, traumatic brain injury, intracranial hemorrhage or severe postpartum hemorrhage. To improve safety, and to address the unwanted clotting risk with FVIIa, CT-001 was engineered for rapid clearance from the blood. This feature reduces the time in which an individual is exposed to pro-coagulant activity, which reduces the risk of thromboembolic events. To improve efficacy, while compensating for the rapid removal of CT-001 from the blood, the molecule has also been engineered to target the site of bleeding more efficiently and effectively than conventional FVIIa, with resultant increase in activity. CT-001 was originally developed by Dr. Hermiston while he served as Vice President of Biologics at Bayer AG and subsequently acquired by the Company. CT-001 is currently under investigation for treatment of severe postpartum hemorrhage.

[1] Centers for Disease Control and Prevention, National Center for Injury Prevention and Control

[2] Tisherman SA et al., Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the resuscitation outcomes consortium.Ann Surg 2015 261:586-590.

[3] Spinella PC et al, Prehospital hemostatic resuscitation to achieve zero preventable deaths after traumatic injury. Curr Opin Hematol 2017 24:529-535.

[4] Sim DS et al., In vitro characterization of CT-001 – a short-acting factor VIIa with enhanced prohemostatic activity. Res Pract Thromb Haemost 2021 5:e12530.

About Coagulant Therapeutics Corporation

Coagulant Therapeutics is a privately held company focused on the design, development and commercialization of therapeutics targeted to the coagulation cascade and its adjacencies. The Company’s lead product candidate, CT-001, is a next-generation Factor VIIa designed for enhanced efficacy and safety in the setting of acute bleeding. Coagulant is also developing additional therapeutics for the treatment of acute bleeding and other coagulation cascade-related diseases. Founded in 2019, the company is based in Berkeley, California. For more information, please visit www.coagulanttherapeutics.com.