Cardior Announces First Patient Dosed in
Phase 2 Study Evaluating Efficacy and Safety of Non-coding RNA-Based Lead Candidate CDR132L in Heart Failure Patients Post-Myocardial Infarction
Hanover, Germany, July 20, 2022 – Cardior Pharmaceuticals, a clinical-stage biotech
company developing non-coding RNA (ncRNA)-based therapeutics for patients with cardiac
diseases, today announced the dosing of the first patient in their multicenter Phase 2 trial
assessing efficacy and safety of CDR132L in 280 patients with reduced left ventricular ejection
fraction after myocardial infarction (HF-REVERT). CDR132L is an oligonucleotide-based
ncRNA inhibitor that targets microRNA-132, a central regulator of pathological cardiac
remodeling processes. Cardiac remodeling is a debilitating and often life-threatening
consequence of myocardial infarction that contributes to the development of heart failure.
Myocardial infarction (MI), commonly known as a heart attack, is an extremely severe condition
caused by a blockage in the coronary arteries limiting the blood supply to the heart. Even if
resolved, MI can lead to permanent damage of the heart cells initiating pathological cardiac
remodeling resulting in the development of heart failure. Heart failure remains one of the
leading causes of death globally with only limited intervention options. Cardior’s lead candidate
is designed to address the root cause of the pathological remodeling of the heart following MI
to halt and reverse the detrimental signaling cascade and restore normal function of the heart.
CDR132L is the first-ever ncRNA-based therapy to enter Phase 2 studies in heart disease.
CDR132L’s target is the well-established microRNA, miR-132, which plays a key role in
pathological cardiac remodeling processes. Levels of miR-132 are elevated in the cardiac
tissue of heart failure patients, triggering well-defined molecular pathways. Inhibition of miR132 by CDR132L normalizes those pathways leading to a transformational change at the
tissue level aiming to restore normal cardiac muscle function.
“RNA therapies have a tremendous potential to fundamentally change the treatment paradigm
for many diseases. Achieving Phase 2 initiation for CDR132L marks a meaningful step towards
validating a disease-modifying therapeutic that inhibits a master regulator of cardiopathology.
This innovation is based on our in-depth expertise in developing non-coding RNA-based
treatments,” said Rahul Agrawal, MD, Chief Medical Officer of Cardior. “Our antisense
oligonucleotide-based inhibitor addresses key molecular mechanisms to prevent or reverse
heart failure following myocardial infarction and we look forward to documenting the impact it
can provide to improve patients’ quality of life and reduce mortality.”
HF-REVERT (NCT05350969) is a multicenter, randomized, parallel, three-arm, placebocontrolled clinical proof-of-concept study designed to evaluate the safety and efficacy of
CDR132L in 280 patients with heart failure and reduced left ventricular ejection fraction (LVEF)
after MI. The study consists of a 6-month double-blind period, and a 6-month extension period.
Patients enrolled in the Phase 2 study will be randomized to receive three intravenous
CDR132L infusions at either 5 mg/kg, 10 mg/kg or placebo, administered 28 days apart as an
add-on to Standard of Care (SoC) treatment.
The primary endpoint of the study is defined as percentage change from baseline in the left
ventricular end-systolic volume assessed by echocardiography (ECHO). The left ventricular
end-systolic volume index is used as a clinical assessment of the systolic function of the heart.
Additional outcome measures include changes in biomarkers such as NT-proBNP, as well as
safety assessments including frequency of adverse events and quality of life questionnaires.
The study will be conducted at locations across Europe involving approximately 60 clinical
study centers. The Phase 2 HF-REVERT trial has been designed in collaboration with
Cardior’s Scientific Advisory Board including renowned cardiology experts Prof. Johann
Bauersachs, who is also the trial’s coordinating investigator, and Prof. Scott Solomon, CoChair of the trial. Cardior will initiate subsequent clinical trials for CDR132L in the U.S. following
discussions with the U.S. Food and Drug Administration (FDA).
“Cardior has focused exclusively on meeting this clinical development milestone and reaching
the next stage of our development as a leader in ncRNA therapeutics. By applying our insight
on using ncRNA through an unprecedented mechanism of action that transcends the cellular
level to modulate well-defined pathways, our goal is to move closer to a curative approach for
cardiac diseases. Dosing the first patient in the Phase 2 HF-REVERT study is a first step that
could enable the treatment of other indications including ischemic heart failure and genetic
cardiomyopathies,” commented Claudia Ulbrich, MD, CEO and Co-Founder of Cardior. “I
would like to thank the Cardior team and the clinicians involved in the HF-REVERT trial for the
collaboration that has brought us to this trial initiation and another step closer to addressing a
large and growing unmet medical need.”
“The Phase 2 clinical proof-of-concept study builds upon the promising results from our
Phase 1b clinical study that demonstrated not only a favorable safety profile but also beneficial
cardiac effects in heart failure patients treated with CDR132L versus placebo. The data to date
paved the way for our ncRNA approach as the first therapy to reverse cellular pathology and
potentially restore normal function in millions of cardiac disease patients,” added Prof. Dr. Dr.
Thomas Thum, CSO and Founder of Cardior. “It is exciting that we have moved from
candidate selection to Phase 2 initiation within just five years and we look forward to leveraging
the Phase 2 trial in preparations of a future pivotal trial as well as exploring the further potential
in additional indications.”
About Heart Failure
Heart failure (HF) is a common complication of myocardial infarction and is a result of multiple
structural and functional abnormalities that result in the failure of the heart to pump blood
through the body. The global burden of HF is significant, with an estimated prevalence of >60
million cases. Post-MI HF is associated with a high risk of death with an estimated median
survival of only 4 years and thus represents a high burden for patients and their quality of life.
CDR132L is a synthetic antisense oligonucleotide-based inhibitor directed against the
microRNA-132 (miR-132), that is up-regulated in cardiac tissue of heart failure patients leading
to a pathological expression of genes that are crucially involved in cardiac function thus leading
to pathological remodeling. By blocking miR-132 with its selective inhibitor CDR132L, Cardior
is able to restore healthy levels of miR-132 and trigger a concerted therapeutic effect against
key hallmarks of heart disease including pathological remodeling processes, impaired
contractility and fibrosis. CDR132L has the potential to restore heart function thereby
prolonging the patient’s life span as well as improving quality of life. The candidate is currently
under evaluation in the company’s Phase 2 HF-REVERT trial and has successfully completed
Phase 1b clinical studies demonstrating a favorable safety profile and beneficial cardiac effects
in heart failure patients. Results were published in the European Heart Journal in 2021.
Cardior Pharmaceuticals is a leading clinical-stage biopharmaceutical company pioneering the
discovery and development of RNA-based therapeutics designed to prevent, repair and
reverse diseases of the heart. Cardior’s therapeutic approach uses distinctive non-coding
RNAs as an innovative platform for addressing the root causes of cardiac dysfunctions. The
company aspires to bring transformative therapeutics and diagnostics to patients and thereby
make a lasting impact on the treatment of cardiac diseases worldwide.
Contact for Cardior
Dr. Claudia Ulbrich / Barbara Gaertner-Rupprecht
Cardior Pharmaceuticals GmbH
Phone: +49 511 33 85 99 30
Eva Mulder or Charlotte Spitz
Phone: +49 (0) 171 35 12 733