HIT drives immune-mediated thrombosis; current therapies fail to address underlying platelet activation pathways.
HIT is a serious immune-mediated reaction to heparin that paradoxically increases the risk of thrombosis despite a drop in platelet count.
HIT occurs when antibodies activate platelets, triggering widespread clot formation in veins and arteries. Thrombotic complications affect a large proportion of patients and are the primary cause of illness and death in HIT. Recent clinical and translational research continues to reinforce the urgent need for safer, more targeted therapies that address the immune-driven platelet activation underlying this disease.
Recent findings reported in a 2025 American Society of Hematology (ASH) abstract by Shatzel et al. and in a 2025 publication by Ramadan et al. highlight the high incidence and clinical burden of thrombotic complications in HIT, even with current standard-of-care anticoagulation. These data emphasize the limitations of existing therapies, which primarily inhibit coagulation pathways but do not directly modulate the platelet immune responses central to HIT pathophysiology.
Growing scientific evidence has identified 12-lipoxygenase (12-LOX) as a key mediator of platelet activation and immune thrombotic responses. Foundational work by McKenzie et al. (2022) significantly advanced the understanding of 12-LOX signaling in platelet-driven immune thrombosis, including in HIT, supporting the enzyme as a compelling therapeutic target. Historically, however, drug development efforts targeting 12-LOX have been hindered by a lack of selectivity, raising concerns about off-target effects and safety. This challenge has limited the clinical translation of earlier 12-LOX inhibitors.
The Problem
Deadly Immune Complication of Heparin
Heparin is the most widely used in-hospital anticoagulant, with over 12 million patients receiving it in the United States each year. Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening immune-mediated complication of heparin administration that occurs when antibodies to heparin activate platelets, leading to clots throughout the circulatory system, dramatically lowering platelet counts, and increasing the risk of bleeding. Complications of HIT include deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, amputation, and death, with mortality rates for HIT exceeding 20% in some studies. CAD-1005 is the only treatment in clinical development that targets the underlying immune drivers of HIT.
Our Solution
CAD-1005 Targets HIT’s Immune Root Cause
CAD-1005 is designed to selectively inhibit 12-LOX, a pathway integral to the primary immune mechanisms driving HIT. Unlike existing therapies for HIT, which are only directed at preventing thrombotic complications, this approach addresses the primary underlying cause of HIT. In preclinical models of HIT, CAD-1005 has been shown to prevent or treat HIT and halt the development of both thrombocytopenia and blood clots. The drug has not been associated with increased bleeding in animals or healthy human volunteers.