AZD3366 / AstraZeneca, APT Therap - LARVOL DELTA

Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo-Controlled Study. (PubMed, J Am Heart Assoc) - P1 | "AZD3366 was well tolerated in healthy participants and demonstrated substantial and durable inhibition of platelet aggregation after single dosing. Higher doses prolonged capillary bleeding time without detectable changes in ex vivo thromboelastometric parameters."

Combination therapy • Journal • P1 data • PK/PD data • Cardiovascular • CNS Disorders

Recombinant human soluble domain of CD39L3 and ticagrelor: cardioprotective effects in experimental myocardial infarction. (PubMed, Eur Heart J) - "Infusion of AZD3366 on top of ticagrelor leads to enhanced cardioprotection compared with ticagrelor alone."

Journal • Cardiovascular • Myocardial Infarction • CD73 • ENTPD1 • PSAP

Safety, Pharmacokinetics, and Pharmacodynamics of AZD3366 Alone and in Combination With Aspirin and Ticagrelor in Healthy Subjects (AHA 2022) - P1 | "AZD3366 alone or in combination with aspirin and ticagrelor was generally safe, well tolerated, and achieved complete platelet inhibition with a dose-dependent duration."

Clinical • Combination therapy • PK/PD data • Cardiovascular • Hematological Disorders • Ischemic stroke • Myocardial Infarction • Reperfusion Injury • Thrombosis

Administration of a human recombinant apyrase (AZD3366) limits myocardial tissue injury and improves cardiac function in a pig model of STEMI assessed by serial CMR (ESC 2022) - "Infusion of one single dose of the soluble recombinant apyrase AZD3366 prior to reperfusion exerts cardioprotection by reducing oedema formation, microvascular obstruction and necrosis and improving cardiac performance at rest and after dobutamine stress during the acute post-MI period. Administration of AZD3366 as an adjunctive therapy to standard of care for STEMI patients undergoing primary PCI may reduce myocardial tissue injury."

Preclinical • Cardiovascular • ENTPD1

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AZD3366 in Healthy Subjects, Japanese and Chinese Subjects (clinicaltrials.gov) - P1 | N=103 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | Trial completion date: May 2022 ➔ Jan 2022 | Trial primary completion date: May 2022 ➔ Jan 2022

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • TNFA

Recombinant Apyrase (AZD3366) Against Myocardial Reperfusion Injury. (PubMed, Cardiovasc Drugs Ther) - "AZD3366 attenuated inflammation, necrosis, necroptosis, and pyroptosis and limited IS. The effects of AZD3366 and ticagrelor were additive."

Journal • Cardiovascular • Immunology • Inflammation • Myocardial Infarction • Reperfusion Injury • IL15 • IL6 • RIPK1

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AZD3366 in Healthy Subjects, Japanese and Chinese Subjects (clinicaltrials.gov) - P1; N=107; Recruiting; Sponsor: AstraZeneca; N=82 ➔ 107

Clinical • Enrollment change • Cardiovascular • TNFA

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AZD3366 in Healthy Subjects (clinicaltrials.gov) - P1; N=82; Recruiting; Sponsor: AstraZeneca; Trial completion date: Sep 2021 ➔ Jan 2022; Trial primary completion date: Sep 2021 ➔ Jan 2022

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • TNFA

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AZD3366 in Healthy Subjects (clinicaltrials.gov) - P1; N=87; Recruiting; Sponsor: AstraZeneca; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular • TNFA

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AZD3366 in Healthy Subjects (clinicaltrials.gov) - P1; N=87; Not yet recruiting; Sponsor: AstraZeneca

Clinical • New P1 trial • Cardiovascular • TNFA

Modulation of CD39 and exogenous APT102 correct immune dysfunction in experimental colitis and Crohn’s disease. (PubMed, J Crohns Colitis) - "hCD39 overexpression ameliorated experimental colitis and prevented hypoxia-related damage in vivo. Exogenous administration of APT102 boosted AhR-mediated regulatory effects in vivo while enhancing Treg functions in Crohn's disease in vitro."

Journal • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • AHR

Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging. (PubMed, Korean J Radiol) - "APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Myocardial Infarction • Myocardial Ischemia • Reperfusion Injury

[VIRTUAL] Administration of a soluble ADPase, AZD3366, on top of ticagrelor confers additional cardioprotective benefits to that of ticagrelor alone (ESC 2020) - "Infusion of a soluble recombinant ADPase (AZD3366) on top of ticagrelor leads to a greater cardioprotection as compared to ticagrelor alone. Co-administration of both drugs in AMI patients undergoing revascularization deserves to be investigated."

Cardiovascular • Myocardial Infarction • CD73

AZD3366-an Optimized Recombinant Human Apyrase Combining Anti Platelet, Anti Inflammatory and Tissue Protective Actions With Low Bleeding Risk for Potential Mitigation of Thromboembolic Complications (AHA 2019) - "Tail bleeding and platelet aggregation inhibition were studied in anesthetized mice iv administered vehicle, AZD3366, ticagrelor or AZD3366 and ticagrelor in combination. Moeckel et al 2014. Sci Transl Med;6:248ra105."

IL1B