CDR 132L / Hannover Medical School, Cardior Pharma - LARVOL DELTA

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=294 | Completed | Sponsor: Cardior Pharmaceuticals GmbH | Active, not recruiting ➔ Completed

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

Novo Nordisk Gets CDSCO Panel Nod To study CDR132L (Medical Dialogues) - "Novo Nordisk has got the go-ahead from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct the clinical trial of CDR132L 45.2 (45,2) mg/vial, a synthetic oligonucleotide that's being developed to treat heart failure. This came after Novo Nordisk presented phase 2 clinical study protocol no. NN6706-8282 version 1.0 dated 21 November 2024."

New P2 trial • Heart Failure

Exploring the role of pericardial miRNAs and exosomes in modulating cardiac fibrosis. (PubMed, Cardiovasc Pathol) - "Presenting the first human miRNA antisense drug trial, inhibition of miR-132 by intravenous administration of a novel antisense oligonucleotide, CDR132L, established efficacy in reducing miR-132 in plasma samples in a dose-dependent manner. We screened the literature, provided an overview of the miRNAs and exosomes present in PF, and drew a connection to those miRNAs previously elucidated in cardiac fibrosis and HF. Further, we speculate about clinical implications and potential delivery methods."

Journal • Review • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Ventricular Tachycardia • IL2RG • MIR132

REMOD-REVERT: Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Cardior Pharmaceuticals GmbH | N=130 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Cardiovascular • Congestive Heart Failure • Heart Failure

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=294 | Active, not recruiting | Sponsor: Cardior Pharmaceuticals GmbH | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2024 ➔ Sep 2024

Enrollment closed • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial. (PubMed, Eur J Heart Fail) - "The HF-REVERT trial may underpin the concept of miR-132 inhibition to prevent or reverse cardiac remodelling in post-MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • IL2RG • MIR132

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=280 | Recruiting | Sponsor: Cardior Pharmaceuticals GmbH | Trial completion date: Nov 2024 ➔ Apr 2025

Trial completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

REMOD-REVERT: Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Cardior Pharmaceuticals GmbH | Trial completion date: May 2025 ➔ Sep 2025 | Initiation date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: May 2025 ➔ Sep 2025

Trial completion date • Trial initiation date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

microRNA-132 Inhibition Improves Cardiac Function and Reduces Remodeling in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF): An Exploratory Subgroup Analysis of the CDR132L First-in-Human Study (AHA 2023) - "Analysis of the HFrEF subgroup in this FiH trial, although limited by the small patient numbers, indicatively underlines the encouraging benefits of CDR132L, a novel antisense drug, on LV function and cardiac remodeling as established in previous large animal HF models."

Clinical • P1 data • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • IL2RG • LCN2 • MIR132

Plasma miR-132 Serves as a Blood Biomarker for Monitoring Treatment Efficacy of miR-132 Targeting Drugs Using a Novel CE-Marked Kit System (AHA 2023) - P1 | "Plasma miR-132 was validated as a suitable target engagement and therapy monitoring biomarker and the newly developed CE-marked kit "CardiorHealth miR-132 Plasma PCR Kit (IVD)" fulfilled its intended use to quantify plasma miR-132 and can be used for monitoring treatment with drugs targeting miR-132."

Biomarker • Clinical • Cardiovascular • Myocardial Infarction • IL2RG • KEAP1 • MIR132

miR-132 Inhibition Shows Anti-Hypertrophic Effects in Preclinical Heart Failure Models and in Exploratory Pharmacodynamic Parameters of a First-in-Human Phase 1b Clinical Trial (AHA 2023) - P1 | "Our results confirm beneficial effects of CDR132L treatment on pathological cardiac remodeling in HF."

P1 data • PK/PD data • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • IL2RG • LCN2 • MIR132

miR-132 Inhibitor CDR 132L Attenuates Cardiac Remodeling by Exhibiting Anti-Fibrotic Effects (AHA 2023) - P1 | "By blocking aberrant miR-132 expression, CDR132L is capable to halt and reverse pathological cardiac remodeling partly due to its anti-fibrotic effects."

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Myocardial Infarction • IL2RG • MIR132

The Novel Antisense Oligonucleotide CDR132L Improves Cardiac Function in Heart Failure Across Different Species (AHA 2023) - "Pharmacological miR-132 inhibition by CDR132L improved cardiac function in multi-species models of HF, highlighting the therapeutic potential for clinical use in HF patients."

Cardiovascular • Congestive Heart Failure • Heart Failure • IL2RG • MIR132

Efficacy and Safety of miR-132 Inhibitor CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction: Rationale for and Design of the HF-REVERT Trial (AHA 2023) - P2 | "This trial may therefore underpin the concept of miR-132 inhibition to prevent/reverse cardiac remodeling in HF patients. The results will inform the design of a subsequent outcome trial to test the effect of CDR132L in HF patients."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • IL2RG • MIR132

miR-132 Inhibition Improves Myocardial Strain in a Large Animal Model of Chronic Adverse Remodeling (AHA 2023) - "LV and LA motion and contractility were improved by repeated dosing of CDR132L with monthly frequency in a large animal model of chronic post-MI HF. The results highlight the translational value and usability of MRI-based cardiac strain imaging in HF drug development and support further clinical development of CDR132L."

Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Myocardial Infarction • IL2RG • MIR132

REMOD-REVERT: Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Cardior Pharmaceuticals GmbH

New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=280 | Recruiting | Sponsor: Cardior Pharmaceuticals GmbH | Not yet recruiting ➔ Recruiting

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

Different Effects on Protein Expression of CDR132L, an Antisense Inhibitor of miR-132, and Standard Therapies for Myocardial Infarction. (PubMed, Front Cardiovasc Med) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • MIR132

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=280 | Not yet recruiting | Sponsor: Cardior Pharmaceuticals GmbH

New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

"Yes, absolutely interesting approach. ➡️ Preparations for Phase Il study with CDR132L are ongoing‼️" (@JBauersachsMD)

MicroRNA-Related Strategies to Improve Cardiac Function in Heart Failure. (PubMed, Front Cardiovasc Med) - "Further, we summarize the opportunities and challenges for HF-related miRNA therapeutics targets, and discuss the first clinical trial of an antisense drug (CDR132L) in patients with HF. Finally, we outline current and future challenges and potential new directions for miRNA-based therapeutics for HF."

Journal • Review • Cardiovascular • Congestive Heart Failure • Developmental Disorders • Heart Failure

Advances in miR-132-Based Biomarker and Therapeutic Potential in the Cardiovascular System. (PubMed, Front Pharmacol) - "Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease."

Biomarker • Journal • Review • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Fibrosis • Heart Failure • Immunology • MIR132

[VIRTUAL] Rationale for CDR132L, an antisense inhibitor of miR-132, for a novel therapy for ventricular remodelling after myocardial infarction (ESC 2021) - "CDR132L might have an additive or synergistic action to standard drugs, given the different effects on protein expression profiles. CDR132L might then help prevent post-MI remodelling even on top of optimal medical therapy. This point should be verified in dedicated studies."

Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • CD44 • EIF4G1 • GATA3 • GPX1 • HMOX1 • LIFR • MIR132 • PRDX1

[VIRTUAL] Novel antisense therapy targeting microRNA-132 in patients with heart failure (ESC 2021) - "This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • MIR132

"Worl-wide first study of an oligonucleotide therapeutics in #HF 👤 🛑 miR-132 w/ CDR132L @_ThomThum_#ESCGenomics @escardio Promising new therapeutics!" (@FranBermudz)

MIR132