zalanfiban (RUC-4) / CeleCor - LARVOL DELTA

Mass balance and metabolite profiling of 14C-Zalunfiban in humans following single-dose subcutaneous administration. (PubMed, Xenobiotica) - "Total dose recovery reached >90% by 240 hours.Zalunfiban is rapidly metabolized to the nearly inactive M1 metabolite, which is excreted primarily in urine. Renal impairment, therefore, is unlikely to significantly prolong zalunfiban effects and dose adjustment in patients with reduced renal function may not be required."

Journal • Renal Disease

Zalunfiban at First Medical Contact in Patients with ST-Segment Elevation Myocardial Infarction (AHA 2025) - P3 | "Coronary blood flow was significantly faster in the zalunfiban treated group on arrival to the cardiac catheterization laboratory (median 109 vs 176 frames, P=0.012).CONCLUSIONSAmong early-presenting STEMI patients, a single subcutaneous injection of zalunfiban at first medical contact significantly improved pre-intervention infarct related artery patency and reduced the likelihood of a worse clinical endpoint at 30 days without an increase in severe or life-threatening bleeding. (Funded by CeleCor Therapeutics, CELEBRATE ClinicalTrials.gov number, NCT04825743)"

Clinical • Late-breaking abstract • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Myocardial Infarction • Thrombosis

Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction. (PubMed, NEJM Evid) - P3 | "In patients with STEMI, zalunfiban administered at first medical contact significantly improved preintervention infarct-related patency and reduced the likelihood of a worse 30-day multicomponent hierarchical clinical end point. Zalunfiban was not associated with increased severe or life-threatening bleeding but was associated with increased mild to moderate bleeding. (Funded by CeleCor Therapeutics; CELEBRATE ClinicalTrials.gov number, NCT04825743)."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Myocardial Infarction • Thrombosis

CELEBRATE: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (clinicaltrials.gov) - P3 | N=2463 | Active, not recruiting | Sponsor: CeleCor Therapeutics | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: May 2025 ➔ May 2026 | Completed ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Myocardial Infarction

CELEBRATE: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (clinicaltrials.gov) - P3 | N=2463 | Completed | Sponsor: CeleCor Therapeutics | Recruiting ➔ Completed | Trial completion date: Apr 2026 ➔ May 2025

Trial completion • Trial completion date • Cardiovascular • Myocardial Infarction

CELEBRATE: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (clinicaltrials.gov) - P3 | N=2499 | Recruiting | Sponsor: CeleCor Therapeutics | Trial completion date: Dec 2024 ➔ Apr 2026 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Cardiovascular • Myocardial Infarction

Greater Coronary and Myocardial Perfusion, and Lower Thrombus Burden at Initial Angiogram with Increasing Doses of Zalunfiban in Patients with STEMI (CVCT USA 2024) - No abstract available

Clinical • Thrombosis

Pharmacokinetics of 14C-Labeled Zalunfiban (RUC-4) Suggests That No Dose Adjustment Is Necessary for Impaired Renal Function (TCT 2024) - No abstract available

PK/PD data • Chronic Kidney Disease

Current and Future Roles of Glycoprotein IIb-IIIa Inhibitors in Primary Angioplasty for ST-Segment Elevation Myocardial Infarction. (PubMed, Biomedicines) - "The ongoing CELEBRATE trial, including 2499 STEMI patients, may potentially provide compelling data to support the upstream treatment of STEMI patients undergoing mechanical reperfusion. In fact, although the current therapeutic target of increased rates of timely reperfusion has been achieved, the future goal in myocardial infarction treatment should be to achieve the most rapid reperfusion prior to primary percutaneous coronary intervention, thus further minimizing myocardial damage, or, in some cases, even preventing it completely, and improving survival."

Journal • Review • Cardiovascular • Hematological Disorders • Myocardial Infarction • Thrombosis

Zalunfiban: A Review of Current Knowledge and Future Applications of an Innovative Antiplatelet Agent. (PubMed, Cardiol Rev) - "It has shown to be safe and effective in both phase 1 and phase 2 trials and is under investigation in phase 3 trials. In this review, we discuss zalunfiban in detail, including its mechanism of action, adverse effects, current recommendations for use, and ongoing trials."

Journal • Review • Cardiovascular • Myocardial Infarction

Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s). (PubMed, J Am Heart Assoc) - "Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbβ3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban...It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second-generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI-associated thrombocytopenia."

Journal • Review • Hematological Disorders • Thrombocytopenia

In vitro comparison of platelet aggregation between zalunfiban and selatogrel in healthy donors (ESC 2023) - "Whole blood from healthy donors not taking aspirin (N=10) was anticoagulated with 3.2% TSC and 100 μM PPACK...Conclusion Selatogrel is a potent inhibitor of ADP-induced platelet aggregation, but has low impact on TRAP-induced platelet aggregation, whereas zalunfiban is a potent inhibitor of both ADP and TRAP-induced platelet aggregation. The difference between the drugs needs to be considered in light of the known generation of thrombin at the site of vascular injury within seconds."

Preclinical • Cardiovascular

Comparison of the effects of the GPIIb-IIIa antagonist Zalunfiban and the P2Y12 antagonist Selatogrel on Platelet Aggregation. (PubMed, J Thromb Thrombolysis) - "An example is the antithrombotic treatment of acute coronary syndrome (ACS), in particular ST-elevated myocardial infarction (STEMI) patients who are in need for rapid acting strong antithrombotic therapy despite the use of aspirin and oral P2Y12-inhibitors...Zalunfiban also had greater inhibition of MA in response to TRAP at the Cmax dose. These data suggest that zalunfiban may provide greater protection in reducing thrombus formation than selatogrel, especially since thrombin is an early, key primary agonist in the pathophysiology of thrombotic events."

Journal • Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction • Thrombosis

Pre-Percutaneous Coronary Intervention Zalunfiban Dose-Response Relationship to Target Vessel Blood Flow at Initial Angiogram in ST-Elevation Myocardial Infarction - A Post Hoc Analysis of the Cel-02 Phase IIa Study. (PubMed, Am Heart J) - "This post hoc analysis found that higher doses of zalunfiban administered in the cardiac catheterization lab prior to vascular access were associated with greater coronary and myocardial perfusion, and lower thrombus burden at initial angiogram in patients with STEMI undergoing primary percutaneous coronary intervention."

Journal • P2a data • Retrospective data • Cardiovascular • Myocardial Infarction • Thrombosis

Dual Antiplatelet Therapy with Parenteral P2Y Inhibitors: Rationale, Evidence, and Future Directions. (PubMed, J Cardiovasc Dev Dis) - "Dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and an inhibitor of the platelet P2Y receptor for ADP, remains among the most investigated treatments in cardiovascular medicine...The latter have been shown to be extremely suitable in drug-naïve patients with acute coronary syndrome (ACS), mainly because oral P2Y inhibitors are associated with delayed efficacy in patients with STEMI and because pre-treatment with P2Y inhibitors is discouraged in NSTE-ACS, and in patients with recent DES implantation and in need of urgent cardiac and non-cardiac surgery. More definitive evidence is needed, however, about optimal switching strategies between parenteral and oral P2Y inhibitors and about newer potent subcutaneous agents that are being developed for the pre-hospital setting."

Journal • Review • Acute Coronary Syndrome • Cardiovascular • Hematological Disorders • Thrombosis

CELEBRATE: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (clinicaltrials.gov) - P3 | N=2499 | Recruiting | Sponsor: CeleCor Therapeutics | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial primary completion date • Cardiovascular • Myocardial Infarction

Pre-hospital treatment with zalunfiban (RUC-4) in patients with ST- Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Rationale and design of the CELEBRATE trial. (PubMed, Am Heart J) - P3 | "The CELEBRATE trial will assess whether a single pre-hospital subcutaneous injection of zalunfiban in addition to standard-of-care in patients with STEMI with intent to undergo primary PCI will result in improved clinical outcome."

Clinical • Journal • Cardiovascular • Myocardial Infarction

Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions. (PubMed, Thromb Haemost) - "Novel parenteral antiplatelet drugs, such as cangrelor, selatogrel, and zalunfiban, have been recently developed to achieve rapid, potent antiplatelet effects while preserving hemostasis. We provide a description of currently available parenteral antiplatelet agents and of those in clinical development for prehospital administration in STEMI patients."

Journal • Cardiovascular • Hematological Disorders • Myocardial Infarction • Thrombocytopenia

CELEBRATE: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (clinicaltrials.gov) - P3 | N=2499 | Recruiting | Sponsor: CeleCor Therapeutics | Phase classification: P2b ➔ P3 | N=1668 ➔ 2499 | Trial completion date: Jun 2023 ➔ Dec 2024 | Trial primary completion date: Mar 2023 ➔ Dec 2023

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Cardiovascular • Myocardial Infarction

[VIRTUAL] Assessing the Pharmacodynamics of RUC-4 (Zalunfiban), a Novel αIIbβ3 Antagonist, Using VerifyNow Assays in Patients with ST-Segment Elevation Myocardial Infarction (STEMI) Treated with Aspirin and Ticagrelor (ISTH 2021) - "Over the next 3 hours, as RUC-4’s blood concentration decreased (Table) and ticagrelor’s effects increased, the ADP assay remained inhibited, the Base assay returned to pre-treatment levels, and the iso-TRAP assay returned toward pre-treatment levels, but not as completely as with the Base assay, reflecting modest inhibition of the iso-TRAP assay by ticagrelor. Conclusions : Combining VerifyNow assays provides important information: 1) the Base assay is best suited for measuring the isolated effect of RUC-4 after co-therapy with ticagrelor, and 2) when the Base assay returns to baseline, the ADP assay provides an accurate assessment of the ticagrelor effect."

Clinical • PK/PD data • Cardiovascular • Myocardial Infarction

CELEBRATE: A Phase 2B Study of RUC-4 in Subjects With ST-elevation MI (clinicaltrials.gov) - P2b; N=1668; Recruiting; Sponsor: CeleCor Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular • Myocardial Infarction

CELEBRATE: A Phase 2B Study of RUC-4 in Subjects With ST-elevation MI (clinicaltrials.gov) - P2b; N=1668; Not yet recruiting; Sponsor: CeleCor Therapeutics

New P2b trial • Cardiovascular • Myocardial Infarction

CEL-02: A Phase 2 Open Label Study to Assess the PK/PD Properties of RUC-4 in Patients With a ST-elevation Myocardial Infarction (clinicaltrials.gov) - P2; N=27; Completed; Sponsor: CeleCor Therapeutics; Recruiting ➔ Completed

Clinical • Trial completion • Cardiovascular • Heart Failure • Myocardial Infarction

CEL-02: A Phase 2 Open Label Study to Assess the PK/PD Properties of RUC-4 in Patients With a ST-elevation Myocardial Infarction (clinicaltrials.gov) - P2; N=24; Recruiting; Sponsor: CeleCor Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular • Heart Failure • Myocardial Infarction

CEL-02: A Phase 2 Open Label Study to Assess the PK/PD Properties of RUC-4 in Patients With a ST-elevation Myocardial Infarction (clinicaltrials.gov) - P2; N=24; Not yet recruiting; Sponsor: CeleCor Therapeutics

Clinical • New P2 trial