Coagulant Therapeutics Presents Data on an Exosite-Specific Nanobody Library to Activated Protein C (APC) at the 2022 American Society of Hematology (ASH) Annual Meeting

Oral presentation describes a unique APC nanobody library and its potential as a source for novel treatments to diseases including trauma, hemophilia, ischemia and sepsis. 

SAN FRANCISCO, Dec. 11, 2022 /PRNewswire/ -- Coagulant Therapeutics Corporation, a privately held company focused on the design, development and commercialization of therapeutics targeted to the coagulation cascade and its adjacencies, announced data from pre-clinical studies on a novel llama-derived antibody (nanobody) library directed to the APC exosite. An oral presentation titled "Selective Modulation of Activated Protein C Activities by an Exosite-Specific Nanobody Library"  will be presented at the American Society of Hematology Annual Meeting in New Orleans, Louisiana, December 10-13, 2022.

"This nanobody library not only offers potential treatments for acute bleeding conditions, such as trauma and hemorrhagic stroke, it also provides the opportunity to identify possible treatments in indications beyond acute bleeding where APC plays an important role, such as hemophilia and sepsis ," said Terry Hermiston, Ph.D., founder and CEO of Coagulant Therapeutics.  Dr. Hermiston pointed out that the different mechanisms of action between the APC-targeting molecules and the companies lead molecule, CT-001, an engineered highly potent, fast clearing FVIIa molecule, suggest that these molecules may actually complement one another in the clinic.  "We are excited to explore their potential as additive or synergistic agents in the treatment of acute bleeds."   

The data, presented by Derek Sim, Ph.D., Chief Scientific Officer for Coagulant Therapeutics, described novel llama-derived nanobodies to the exosite of Activated Protein C (APC) that affected anticoagulation, histone cleavage and receptor mediated cleavage activities of APC.  The characterization resulted in 13 novel activity profiles that can be employed to regulate specific APC functions for therapeutic purposes.

"APC differs from the parent molecule protein C (PC) by the absence of 12 amino acids.   Our hope was to use the unique properties of nanobodies to generate antibodies that selectively inhibit some of the APC associated functions" reported Dr. Sim "and we are very pleased to report the number and surprising diversity of APC-specific nanobodies, exemplified by LP 11, whose activity profile of  hemostasis and cytoprotection promotion make it an appealing candidate for the treatment of Hemophilia and Trauma, respectively." 

In addition to the oral presentation on the APC library, Coagulant presented a poster on their lead molecule, CT-001.

Abstract Title: CT-001, a Rapid Clearing Factor VIIa, Provides Pro-Hemostatic Activity to Reduce Blood Loss in Coagulopathic Conditions Induced by Activated Protein C
Abstract Number: 2458
Session Name: 321. Coagulation and Fibrinolysis: Basic and Translational: Poster II
Session Date: Sunday, December 11, 2022
Presentation Time: 6:00-8:00 PM CST/7:00-9:00 PM EST
Presenter: Dr. Derek Sim
Summary: These data, presented by Derek Sim, Ph.D., the Chief Scientific Officer of Coagulant Therapeutics, suggest that a FVIIa molecule engineered to be both safer and more active than recombinant FVIIa (rFVIIa) can be an effective treatment for acute bleeding, including bleeding with Coagulopathy, broadly defined as a derangement of hemostasis resulting in impaired clot formation.  CT-001 is being developed as a new treatment for severe postpartum hemorrhage, a growing problem and a significant factor in maternal morbidity and mortality not only in the US but globally.  These studies support its potential broader use in coagulopathic settings such as trauma.   

CT-001 is an engineered version of FVIIa that is designed to address the limitations of the recombinant FVIIa (rFVIIa), approved for use in Hemophilia A and B patients with inhibitors, congenital FVII deficiency, and Glanzmann's thrombasthenia with refractoriness to platelet transfusions but not approved in the US 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 rFVIIa, 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 rFVIIa, 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.

APC is a pleiotropic enzyme that has been identified as a target in the treatment of a variety of disease indications including Trauma, Hemophilia, Ischemia and Sepsis.  Coagulant Therapeutics Corporation has initiated a research program into the identification of APC-directed therapeutic antibodies, leveraging the unique features of llama antibodies (nanobodies) to derive novel nanobodies to the exosite of the protein.  The nanobody library has an array of different antibodies to differing epitopes and, importantly, generated a lead which is being studied for treatment of trauma and hemophilia, respectively.  As these nanobodies have a different target and mechanism of action to CT-001, it is anticipated that these can be independent treatments with the potential for additive or synergistic effects to CT-001 in the acute bleeding setting.

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 targeted to APC for the treatment of acute bleeding and other coagulation cascade-related diseases.  Founded in 2019, the company is based in Berkeley, California.

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