AZD2389 / AstraZeneca - LARVOL DELTA

PECHORA: The Phase 1, Open-label, PET Trial Designed to Investigate the Effect of AZD2389 on FAP Occupancy in the Liver in Participants With Advanced Liver Fibrosis. (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: AstraZeneca

New P1 trial • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

BORANA: A Study to Evaluate the Safety, Tolerability, PK, and PD Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis. (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

A Study to Investigate the Pharmacokinetics of AZD2389 in Healthy Participants When Administered Alone and in Combination With Quinidine (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=24 ➔ 16

Enrollment change • Enrollment closed • Hepatology

CRIOLLO: A Study to Investigate How Multiple Oral Doses of AZD2389 Affect the Pharmacokinetics of Midazolam, Caffeine, and Bupropion in Healthy Participants (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=16 ➔ 8

Enrollment change • Enrollment closed • Hepatology

CAMPOLINA: A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD2389 (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Hepatology

A Single and Multiple Ascending Dose Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD2389 in Healthy Participants (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Investigate the Pharmacokinetics of AZD2389 in Healthy Participants When Administered Alone and in Combination With Quinidine (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

A Study to Investigate the Pharmacokinetics of AZD2389 in Healthy Participants When Administered Alone and in Combination With Quinidine (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Hepatology

CRIOLLO: A Study to Investigate How Multiple Oral Doses of AZD2389 Affect the Pharmacokinetics of Midazolam, Caffeine, and Bupropion in Healthy Participants (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Hepatology

CRIOLLO: A Study to Investigate How Multiple Oral Doses of AZD2389 Affect the Pharmacokinetics of Midazolam, Caffeine, and Bupropion in Healthy Participants (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

A Study to Investigate the Pharmacokinetics of AZD2389 When Administered Alone and in Combination With Itraconazole in Healthy Participants (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

First-in-human single and multiple ascending dose study of AZD2389, a potent inhibitor of fibroblast activation protein, in healthy participants to evaluate safety, tolerability, pharmacokinetics and target engagement (EASL 2025) - "In healthy participants, there were no safety or tolerability concerns up to the highest dose of AZD2389 tested in both the SAD and MAD parts. AZD2389 is a selective FAP inhibitor and is being studied further as a treatment for liver fibrosis."

Clinical • P1 data • PK/PD data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • FGF21

A Study to Investigate the Pharmacokinetics of AZD2389 When Administered Alone and in Combination With Itraconazole in Healthy Participants (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: AstraZeneca | N=24 ➔ 16

Enrollment change

A Study to Investigate the Pharmacokinetics of AZD2389 When Administered Alone and in Combination With Itraconazole in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Investigate the Pharmacokinetics of AZD2389 When Administered Alone and in Combination With Itraconazole in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

CAMPOLINA: A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD2389 (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

CAMPOLINA: A Phase I Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD2389 (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Hepatology

BORANA: A Study to Evaluate the Safety, Tolerability, PK, and PD Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis. (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: AstraZeneca

New P2 trial • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

A Single and Multiple Ascending Dose Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD2389 in Healthy Participants (clinicaltrials.gov) - P1 | N=118 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Nov 2024 ➔ Mar 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date

A SMALL MOLECULE INHIBITOR OF FIBROBLAST ACTIVATION PROTEIN (FAP) BLOCKS ENZYMATIC ACTIVITY AND IMPROVES LIVER HISTOPATHOLOGY IN CYNOMOLGUS MONKEYS WITH MASH AND F1/F2 FIBROSIS (AASLD 2024) - " We have developed a potent oral FAP inhibitor AZD2389, which blocks the cleavage of human a2-AP, FGF21 and collagens ex vivo... To our knowledge, this is the first study demonstrating that FAP inhibition leads to increased intact a2-AP in vivo in a physiologically relevant disease model. Importantly, histological improvement of MASH and fibrosis, underline the therapeutic potential of our compound in the treatment of fibrotic liver diseases."

Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FAP • FGF21