Cadrenal Phase 2 data show 25% thrombotic event cut in HIT
Cadrenal Therapeutics presented late-breaking Phase 2 results for its 12-lipoxygenase (12-LOX) inhibitor CAD-1005 at the International Society on Thrombosis and Haemostasis (ISTH) 2026 Congress in Paris on 13 July, reporting an absolute reduction of more than 25 percentage points in new or worsening thrombotic events compared with placebo (50% vs. more than 75% in the control arm) in patients with heparin-induced thrombocytopenia (HIT).
The study is notable as the first randomised, blinded, placebo-controlled clinical trial ever conducted in HIT, a rare but potentially fatal immune-mediated condition in which antibodies against platelet factor 4-heparin complexes trigger uncontrolled platelet activation and clotting. Selected as one of three late-breaking abstracts at a congress that drew over 6,000 registrants, the oral presentation was delivered by principal investigator Dr Steven E. McKenzie.
Trial design and efficacy signal
The Phase 2 study was not powered to reach statistical significance, and Cadrenal was transparent about that limitation. The reported event rates nonetheless produced a clinically meaningful separation between arms. No serious adverse events were attributed to CAD-1005, there were no major bleeding episodes in serotonin-release assay-positive patients, and no deaths were recorded, according to the release.
One finding from the trial that Cadrenal says will inform Phase 3 design is that platelet count recovery, the traditional surrogate endpoint used in HIT studies, proved an inadequate marker of clinical outcome: thrombotic events continued to occur even after platelet counts had normalised. The company says this reframes how a pivotal trial should be designed and measured.
McKenzie said the dataset illustrated how CAD-1005 "could fundamentally shift the treatment paradigm for acute thrombotic care" by addressing the underlying 12-LOX immune signalling loop, rather than simply reducing thrombin generation as existing non-heparin anticoagulants do.
Regulatory status and competitive landscape
CAD-1005 holds Orphan Drug and Fast Track designations from the FDA, and Orphan Drug status from the EMA, providing regulatory incentives that reduce the pivotal trial burden and support accelerated review pathways. Cadrenal describes the programme as Phase 3-ready and has cited a peak annual revenue estimate of approximately $2 billion for the HIT indication, though that figure is a company projection and has not been independently validated.
HIT remains an area with no approved root-cause therapy. Current standard of care relies on alternative anticoagulants such as argatroban and fondaparinux, which manage the downstream coagulation cascade but do not interrupt upstream platelet immune activation. That mechanistic gap is the commercial rationale for CAD-1005, and the Phase 2 data provide the first controlled evidence that 12-LOX inhibition can reduce clinical events in this setting.
The broader competitive landscape in rare thrombotic disorders has become more active in recent years, with several academic and industry groups investigating platelet immunoreceptor signalling. No directly comparable 12-LOX inhibitor appears to be in late-stage development for HIT at this time, though Cadrenal will need to demonstrate statistical efficacy in a properly powered Phase 3 study to support a new drug application.
Chief executive Quang X. Pham said recent financing has positioned the company to advance partnering discussions for both CAD-1005 and tecarfarin, its oral anticoagulant in development for patients with end-stage kidney disease and left ventricular assist devices. The company did not disclose the size or terms of that recent financing in the materials accompanying the ISTH announcement.