Cadrenal presented Phase 2 data at ISTH 2026 showing CAD-1005 reduced thrombotic events in heparin-induced thrombocytopenia without increasing major bleeding, supporting Phase 3 development.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Cadrenal Therapeutics has presented late-breaking Phase 2 clinical data for CAD-1005 (NCT05785819), an investigational 12-lipoxygenase (12-LOX) inhibitor, showing a reduction in thrombotic events among patients with heparin-induced thrombocytopenia (HIT). The findings were delivered during an oral late-breaking presentation at the International Society on Thrombosis and Haemostasis (ISTH) 2026 Congress, marking the first randomized, blinded, placebo-controlled trial conducted in patients with HIT.
The study showed that adding CAD-1005 to standard anticoagulation reduced new or worsening thrombotic events by more than 25% compared with placebo. Although the Phase 2 trial was not powered to demonstrate statistical significance, the results support continued clinical development of the program, which is now considered Phase 3-ready.
CAD-1005 Targets the Underlying Mechanism of HIT
Heparin-induced thrombocytopenia is a rare but potentially life-threatening immune-mediated adverse reaction to heparin therapy. The condition develops when antibodies against platelet factor 4 (PF4)-heparin complexes activate platelets through FcγRIIA receptors, increasing the risk of arterial and venous thrombosis.
Current treatment relies on non-heparin anticoagulants that reduce thrombin generation but do not interrupt the immune-driven platelet activation responsible for disease progression. CAD-1005 inhibits 12-lipoxygenase (12-LOX), an enzyme involved in platelet immune activation and thrombo-inflammatory signaling, offering a different therapeutic approach from existing anticoagulants.
Phase 2 Trial Demonstrated Favorable Efficacy and Safety Signals
The Phase 2 study evaluated CAD-1005 in patients with HIT receiving standard anticoagulation therapy.
Key findings included
- More than a 25% absolute reduction in new or worsening thrombotic events compared with placebo (50% versus more than 75%).
- No serious adverse events attributed to CAD-1005.
- No major bleeding events among serotonin release assay (SRA)-positive patients.
- No deaths reported during the study.
- Reduced thromboembolic events without an increase in major bleeding.
Investigators also reported that platelet count recovery alone did not accurately reflect clinical benefit because thrombotic complications continued after platelet normalization. The findings may help shape endpoint selection for the planned pivotal Phase 3 registration study.
Investigators Highlight Potential Shift in HIT Clinical Development
Principal Investigator Dr. Steven E. McKenzie said the study supports 12-LOX inhibition as a selective strategy that directly interrupts immune-mediated platelet activation in HIT. He noted that the observed reduction in thrombotic events, when combined with standard anticoagulation, suggests CAD-1005 could offer a differentiated treatment option for patients at high risk of thrombosis.
Cadrenal Chief Executive Officer Quang X. Pham said the selection of the study for the ISTH late-breaking session reflects the scientific importance of the findings. He added that the company’s recent financing positions it to advance partnership discussions for both CAD-1005 and tecarfarin.
Regulatory Status and Path Forward
CAD-1005 has received Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration, as well as Orphan Drug designation from the European Medicines Agency.
Cadrenal plans to use the Phase 2 findings to support the design of a pivotal Phase 3 registration trial. With no approved therapies that directly target the immune mechanism underlying HIT, CAD-1005 has the potential to address a significant unmet clinical need if future studies confirm its efficacy and safety.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.