Cadrenal Therapeutics Receives FDA Guidance for Phase 3 Trial of CAD-1005 in HIT

Cadrenal Therapeutics, Inc. (Nasdaq: CVKD) today announced a major regulatory milestone after successfully completing its End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) and receiving guidance on key elements of the Phase 3 pivotal trial for CAD-1005, the Company’s investigational first-in-class 12-lipoxygenase (12-LOX) inhibitor for heparin-induced thrombocytopenia (HIT). Phase 2 data showed a greater than 25% absolute reduction in thrombotic events when CAD-1005 was added to standard anticoagulant therapy.

The meeting with the FDA provided critical guidance on protocol design, study population, dosing, background therapy, exposure, the safety database, and the primary endpoint of new or worsening thrombotic events. After considering FDA feedback, Cadrenal plans to advance directly to a randomized, blinded, placebo-controlled Phase 3 study evaluating CAD-1005 added to the current standard of care for patients with HIT. The planned pivotal Phase 3 study – the first randomized, blinded, placebo-controlled registration trial in HIT – will evaluate CAD-1005 in approximately 120 patients across up to 50 clinical centers worldwide and is intended to support a projected NDA submission in 2029. Patients with suspected HIT will be randomized to CAD-1005 or placebo while receiving standard-of-care anticoagulant therapy and treated for up to 14 days during hospitalization. The primary endpoint – centrally adjudicated – is the incidence of new or worsening thrombotic events in patients with Serotonin Release Assay (SRA)-confirmed HIT, with at least one planned interim analysis.

Heparin is the most widely used in-hospital anticoagulant, with more than 12 million patients receiving it in the United States each year. 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, markedly 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 designed to selectively inhibit 12-LOX, a pathway integral to the primary immune mechanisms that drive HIT, and is the only treatment in clinical development that targets the underlying immune drivers of HIT. CAD-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.

Separately, Cadrenal announced that it plans to initiate a Phase 2a proof-of-concept clinical trial of CAD-1005 to prevent Acute Kidney Injury (AKI) in high-risk patients undergoing cardiac surgery, with the trial expected to begin later this year. Cardiac surgery-associated AKI (CSA-AKI) affects roughly 35,000 U.S. patients each year, represents a potential treatment market estimated at $1 billion annually, and is associated with an approximately 8-fold increase in hospital mortality. There are currently no FDA-approved targeted pharmacologic therapies to prevent CSA-AKI. The planned Phase 2a trial builds on encouraging preclinical data in multiple animal models for CAD-1005 in AKI, as well as existing Phase 1 safety data, and is intended to generate data that may be relevant to Cadrenal’s lead Phase 3-ready program in HIT.

Cadrenal reported a net loss of $3.0 million for the fourth quarter ending December 31, 2025, an improvement compared to a $4.2 million loss in the same period of 2024. The company holds more cash than debt on its balance sheet with a current ratio of 2.72. Its broader pipeline includes tecarfarin, a late-stage oral vitamin K antagonist for patients requiring chronic anticoagulation, and frunexian, a parenteral Factor XIa inhibitor intended for use in acute hospital settings.