Coagulant Therapeutics Announces Publication in Blood Advances Describing Novel Nanobody Library to Activated Protein C (APC) and Initial Leads for Treatment of Trauma and Hemophilia
27 Feb 2023
BERKELEY, Calif., Feb. 27, 2023 /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 the online publication of a manuscript titled "Selective Modulation of Activated Protein C Activities by a Non-Active Site Targeting Nanobody Library" in the journal Blood Advances, a Journal of the American Society of Hematology.
Activated Protect C (APC)APC) has a role in regulating coagulation, inflammation, and cell survival, and thus is important for maintaining the homeostatic balance during health and disease. Developing APC-based therapeutics that selectively eliminate or retain these functions individually, or in combination, has been challenging. Leveraging the unique properties of llama antibodies (referred to as nanobodies) the manuscript describes the generation of a novel nanobody library to APC. The manuscript goes on to demonstrate that by using assays specific for coagulation, inflammation and cell survival functions of APCAPC, the investigators were able to identify an array of human APCAPC specific antibodies able to retain or eliminate these functions. This represents a tool chest for APCAPC targeted therapies that has already identified a lead candidate for the treatment of trauma and hemophilia.
"The ability of the Coagulant Therapeutics APC nanobody library to selectively change the activity profile of APC is quite amazing." said Dr. Laurent Mosnier, Ph.D., Professor in Department of Molecular Medicine at the Scripps Research Institute, and senior author on the publication. "Not only were we able to select for the beneficial activities of APC while eliminating unwanted activities at the same time, but we were also able to improve the cytoprotective effects of APC to enhance the therapeutic properties of this blood coagulation enzyme that is implicated to play a role in many different diseases."
The mechanism of action differs from Coagulant Therapeutics' lead molecule, CT-001, an engineered highly potent, fast clearing FVIIa molecule being developed for the treatment of severe postpartum hemorrhage, the leading cause of maternal mortality globally. As a result, these differing approaches of targeting APC with a nanobody and utilizing a modified coagulation factor may prove to be complementary or even synergistic to one another in the clinic.
"Our novel nanobody library to the human APCAPC protein offers potential treatments for acute bleeding conditions, such as trauma as well as indications beyond acute bleeding where APCAPC play an important role, such as hemophilia and sepsis" said Terry Hermiston, Ph.D., founder and CEO of Coagulant Therapeutics. "APC associated diseases like trauma and sepsis are areas of significant unmet medical need and we view our library and lead molecules as exciting opportunities to explore novel therapies in this space."
About CT-001
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 for use in the acute bleeding settings such as trauma, traumatic brain injury, intracranial hemorrhage or severe postpartum hemorrhage in the US. 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.
About APC Antibody Program
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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