Cadrenal Says New Experimental Therapy Could Change How Doctors Treat Rare Heparin Reaction

Cadrenal Therapeutics, Inc. (NASDAQ:CVKD), a biopharmaceutical company developing transformative therapeutics to overcome the limitations of current anticoagulation therapy, today highlighted the significant and persistent unmet medical need in heparin-induced thrombocytopenia (HIT) and underscored the promise of its recently acquired investigational drug candidate, VLX-1005, the first and only potent, highly selective 12-LOX inhibitor in clinical testing as a potential new treatment option.

Cadrenal Therapeutics acquired VLX-1005 in December 2025, recognizing its potential to transform the treatment landscape for HIT and other immune-mediated thrombotic disorders.

Emerging data from a recent Phase 2 clinical trial evaluating VLX-1005 in individuals with suspected HIT suggest that VLX-1005 may reduce thrombotic complications, supporting its further development as a novel, mechanism-based therapy. Early trial results suggest that selective 12-LOX inhibition may offer a differentiated approach by addressing the immune thrombotic drivers of disease rather than solely suppressing coagulation.

HIT is a serious immune-mediated reaction to heparin that paradoxically increases the risk of thrombosis despite a drop in platelet count. It 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.

VLX-1005 represents a breakthrough in this area. Supported by preclinical and translational studies (Tourdot et al., 2017; Renna et al., 2023), VLX-1005 is the first and only highly selective 12-LOX inhibitor in clinical development. Its selectivity profile is designed to specifically modulate immune-mediated platelet activation while minimizing off-target inhibition of related lipid signaling pathways.

Cadrenal is moving forward rapidly to engage with the U.S. Food and Drug Administration (FDA) to discuss the design of a potential pivotal Phase 3 registration study for VLX-1005 in HIT.

"HIT remains a life-threatening condition with a strikingly high risk of thrombosis despite available therapies," said Quang X. Pham, CEO of Cadrenal Therapeutics. "By selectively targeting 12-LOX, VLX-1005 has the potential to address a core disease mechanism in HIT. We believe this program represents a meaningful opportunity to improve outcomes for patients who currently have limited options."

VLX-1005 has received Orphan Drug Designation (ODD) and Fast Track designation from the U.S. Food and Drug Administration, as well as orphan drug status from the European Medicines Agency. Second-generation oral therapeutics targeting 12-LOX are also under development for type 1 diabetes and other chronic immune-mediated and inflammatory diseases.