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Prevention and mitigation of acute traumatic coagulopathy and bleeding

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL169120-01
Agency Tracking Number: R41HL169120
Amount: $295,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-08-24
Award End Date (Contract End Date): 2024-07-31
Small Business Information
La Jolla, CA 92037-6805
United States
DUNS: 079734119
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (858) 784-2227
Business Contact
Phone: (858) 222-4864
Research Institution
LA JOLLA, CA 92037-1000
United States

 Domestic Nonprofit Research Organization

Project Summary/Abstract
Hematherix is developing superFVa for the treatment of acute traumatic coagulopathy (ATC). Mortality rates with
traumatic hemorrhage often exceed 40%, exposing an unmet clinical need for targeted drug development. ATC
develops early on as the consequence of severe trauma and shock, prior to additional iatrogenic effects. ATC is
distinct from other coagulopathies and is characterized by the selective diminishment of factor V, factor VIII, and
fibrinogen levels due to the exaggerated activation of the protein C and fibrinolytic pathways following vascular
disruption due to trauma and shock. The presence of ATC is associated with uncontrollable bleeding and
increased transfusion requirements, especially during emergency surgery, resulting in increased risks of organ
failure and death. Activated factor V (FVa) is an essential co-factor in the prothombinase complex, enhancing
the rate of thrombin generation approximately 10,000-fold, but is readily inactivated by activated protein C (APC).
SuperFVa is a stable engineered variant of the activated coagulation cofactor factor V and poses a unique targeted
therapy to prevent and correct ATC. Key features of superFVa are its resistance to inactivation by APC due to
mutation of the APC cleavage sites (Arg506/306/679Gln) and its increased specific activity and stability due to
an engineered disulfide link between the A2 and A3 domains. The unique characteristics of superFVa differentiate
it from existing prohemostatic and other experimental anti-APC approaches in development and makes superFVa
inimitably positioned as a targeted strategy for ATC. Data in murine models of ATC support the concept that
APC is a major instigator of ATC. We recently reported that superFVa efficiently prevented ATC when given
prophylactically and corrected ATC when given therapeutically in 2 murine models where ATC was induced
either by trauma and shock or by trauma and bleeding. These data provide strong support for superFVa as a
targeted approach for the treatment of ATC. The objectives for this project are: 1) To provide proof of concept
that correction of ATC by superFVa improves clinically relevant outcomes after trauma such as organ damage and
survival, and 2) To demonstrate that superFVa has a favorable thrombogenicity risk/benefit ratio due to its unique
characteristics. Proof of concept that correction of ATC by superFVa improves survival and organ health outcomes
will have an unprecedented scientific and clinical impact for treatment and rescue of trauma patients with ATC
and provides strong preclinical support for the next IND-enabling development phase of superFVa for treatment of
ATC that will be the subject of a phase 2 application.

* Information listed above is at the time of submission. *

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