Research & Development
Heart Failure Treatment – AnaCardio´s Unique Solution
Heart Failure Treatment – AnaCardio´s Unique Solution
AnaCardio is developing novel inotropic agents with a unique mode-of-action based on the ghrelin signalling pathway, intended to increase contractility without causing adverse tachycardia, arrhythmia, ischemia, or hypotension. The agents increase cardiomyocyte contractility and force, leading to increased cardiac output which can potentially improve organ function, quality of life and functional capacity, and reduce the risk of hospitalization and death. AnaCardio´s treatment concept stems from ground-breaking research from Karolinska Institutet and Founder Professor Lars Lund.
A proof-of-concept study was performed at the Karolinska University Hospital in which 30 out-patients with chronic heart failure were randomized to ghrelin or placebo given intravenously over 120 minutes. The primary outcome measure was cardiac output (CO) at 120 minutes. The ghrelin treated group increased CO significantly by 28%. This was achieved without any signs of arrythmias, tachycardia, ischemia or hypotension.
Furthermore, the ghrelin peptide increased contractility in an ex-vivo model experiment investigating beating mice cardiomyocytes. The observed increase in contractility and force was observed without elevated calcium concentrations and instead achieved by increased calcium sensitization.
Ghrelin peptide study achieved proof-of-concept in 30 HFrEF patients by increasing cardiac output over 120 minutes.
1. Ghrelin increases contractility in beating mouse cardiomyocytes…
2. … without changing Ca2+ transients/concentrations.
3. Ghrelin reduces cAMP levels in cardiomyocytes…
4. … and Ca2+ sensitization occurs through reduction in troponin I phosphorylation.
AC01 is an oral ghrelin peptidomimetic small-molecule – a first in-class calcium sensitizing inotrope. In preclinical studies, AC01 increases contractility/force and sensitizes cardiac cells to calcium, which is differentiated from conventional inotropes that increase calcium concentrations and flux. The latter may cause life-threatening arrythmias and cardiac ischemia. AC01 is the first agent to safely target the underlying mechanism of HFrEF by improving contractility, and as such would potentially have both direct effect on cardiac contractility and organ functions, as well as longer term disease-modifying effects.
Calcium sensitizing inotrope
Based on AC01’s mechanism of action it is viewed by Key Opinion Leaders as a “safe inotrope” that could be used chronically – a holy grail in the field.
Treaters believe that an inotrope that sensitizes cardiac cells to calcium – vs increasing calcium levels – will be safe. This is in contrast to conventional inotropes, which have a desirable effect of increasing the contraction force of the heart but have a negative effect on mortality and are only used as a last resort.
Contractility, Force & Cardiac Output
When considered in context of AC01’s expected safe adverse event profile, doctors identified AC01 as a “safe inotrope”, which would be a true disease modifying therapy that could reverse disease effects – as long as patients stay on therapy chronically.
Small Molecule, oral treatment
As an orally available small molecule, AC01 meets treater’s basic requirements for a novel agent in patients with chronic heart failure.
”The arrhythmias and ischemia we see in conventional inotropes are because of the chronically elevated Ca2+ levels that they cause. This drug will change how sarcomeres themselves react to Ca2+ – potentially avoiding safety concerns”
– HFrEF KOL
”This would be the holy grail. Patients would feel better, have improved blood flow, better system function. This is essentially a safe inotrope – and the only reason we don’t use inotropes more widely is that they worsen outcomes”
– HFrEF KOL
”For chronic patients, oral is what I’m looking for, all the other drugs I use in in these patients are oral. This is in contrast with the inotropes we have now, which we use outpatient in extreme cases and require me to set up patients with infusion pumps. This molecule is much better in many regards”
– HFrEF HVT
GOAL-HF1 – Heart Failure Dose Escalation and 28 day Cohort Expansion Clinical Trial
GOAL-HF1 was a Phase 1b/2a multicentre, randomised, double-blind, placebo-controlled study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AC01 in 58 patients with HFrEF across 14 sites in the Netherlands, United Kingdom, Sweden, and Italy. All patients had NYHA class II–III HFrEF (mean ejection fraction 31.4%), a transvenous implantable cardioverter-defibrillator (ICD) for primary prevention, and were on maximum tolerated guideline-directed medical therapy. Phase 1b consisted of multiple ascending dose escalation in 32 patients across four sequential dose cohorts (0.1–3 mg twice daily, 7 days). In Phase 2a, 26 patients were equally randomised to 1 mg AC01, 3 mg AC01, or placebo orally twice daily for 28 days. More information about the study is available at www.clinicaltrials.gov (NCT05642507).
AC01 appeared safe and well tolerated, with no AC01-related serious adverse events, no deaths, and no treatment discontinuations due to adverse events. There were no apparent signs of tachycardia, new-onset tachyarrhythmias, myocardial ischaemia, morphological or conduction abnormalities, and no cases of symptomatic hypotension. Rapid improvements in cardiac output and stroke volume were observed from Day 1 and sustained through Day 28, consistent with a direct effect on cardiac contractility. There was also an improvement in left ventricular ejection fraction, with a mean increase of +4.8 absolute percentage points at Day 28 in the 3 mg group versus +1.6 percentage points in the placebo group.
The publication, ”Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (GOAL-HF1): a randomised, double-blind, placebo-controlled, phase 1b/2a study”, is available in The Lancet.
AC01, AnaCardio’s lead investigational therapy for heart failure, is backed by a series of seminal publications that together tell the complete AnaCardio story. Together, these papers trace AC01’s effect on cardiac contractility across every stage of development — from isolated heart cells, to animal models, to patients with heart failure. Few cardiac drug candidates can point to this level of mechanistic and translational consistency.
Proof-of-principle with the acyl ghrelin peptide in HFrEF patients, alongside mechanistic mouse studies showing improved cardiomyocyte fractional shortening without calcium mobilization
European Heart Journal, 2023
Mapping AC01’s mechanism of action in mouse cardiomyocytes — contractility gains through Gαi signalling, independent of calcium
Cardiovascular Research, 2025
Hemodynamic and physiological studies showing rapid, sustained improvements in cardiac output and systolic function across HFrEF mice and nonhuman primates
Clinical proof-of-concept for AC01 in our GOAL-HF1 randomised, double-blind, placebo-controlled, phase 1b/2a study in HFrEF patients
The Lancet, 2026
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