Acesion Pharma announces positive phase 2 data from Atrial Fibrillation clinical trial - primary endpoint achieved

First-in-class SK channel inhibition proof of mechanism achieved

First new approach to treating Atrial Fibrillation for 20 years

COPENHAGEN, Denmark, March 14, 2023 /PRNewswire/ -- Acesion Pharma ("Acesion"), the biotech pioneering first-in-class novel therapies for Atrial Fibrillation ("AF"), the most common cardiac arrhythmia, today announced positive data from its Phase 2 trial of AP30663, a first-in-class SK ion channel inhibitor for conversion of AF to normal sinus rhythm.

The trial enrolled 63 patients with a current episode of AF and tested two intravenous doses of AP30663, 3 and 5 mg/kg, compared to placebo. The primary endpoint was the proportion of patients with AF conversion to sinus rhythm within 90 minutes of infusion start. The proportion (conversion rate) for AP30663 5 mg/kg exceeded 50% with no conversions observed for placebo and with a numerical dose-response between the 3 and 5 mg/kg dose. The trial employed a Bayesian analysis and there was a probability (posterior probability) > 99.9% of a true AF conversion rate greater than placebo for each of the two doses. The results from the Bayesian analysis were supported by a traditional analysis of the primary endpoint, demonstrating highly significant P-values for each of the two doses compared to placebo.

The safety profile was consistent with that observed in two previous phase 1 trials with AP30663. The treatment was well tolerated, with no serious adverse events (AEs) reported in the AP30663 groups. The main safety concern with currently available AF drugs - ventricular arrhythmias - were not seen in the trial. A transient increase in the ECG QTc interval compared to placebo was seen with both doses. This increase in QT interval was less than, or comparable to, what is seen with some currently available drugs. Based on non-clinical studies with AP30663, as well as human genetic data, the QT effect can be ascribed to a compound-specific off-target inhibition of the hERG ion channel.

Acesion is advancing an oral SK channel inhibitor program for chronic maintenance treatment to prevent AF recurrence, using a 2^nd generation molecule with higher specificity that avoids ventricular effects, including hERG channel inhibition, while maintaining efficacy in preclinical models.

AF is the most common type of cardiac arrhythmia and is forecast to affect 24 million people in the US and EU by 2030. Acesion is advancing the first new approach to treating AF for decades. It has a pipeline of novel, first-in-class, orally available, small molecules that inhibit the SK channels. In pre-clinical studies, inhibiting the SK channels has been shown to result in pronounced antiarrhythmic effects in the atria while avoiding effects on the ventricles, the major chambers of the heart. Furthermore, the SK channel has strong genetic validation, with genes encoding the SK channels having one of the strongest associations to AF in human genome-wide association studies.

Acesion builds on 20 years of know-how with development of small-molecule SK inhibitors and is the world leader in the field of SK channel inhibition, being the only company able to identify and progress SK channel inhibitors into clinical trials.

Anders Gaarsdal Holst, MD, PhD, Chief Executive Officer of Acesion, said: "This clinical trial has proven the general mechanism of action of SK channel inhibition for treatment of Atrial Fibrillation. It further de-risks our pipeline of small molecule SK inhibitors, including AP31969, our ongoing 2^nd generation oral lead program, which targets the much broader and chronic treatment indication of sinus rhythm maintenance and which is planned to start Phase 1 in H2 2023."

Jørgen Søberg Petersen, MD, PhD, MBA, Chairman of the Board of Directors and Partner at Novo Holdings A/S, said: "With these impressive, first-in-class, clinical proof-of-concept data, we are very excited to see the pioneering efforts of Acesion coming to fruition. With clinical proof-of-concept data on the 1^st generation molecule, Acesion has significantly de-risked their SK channel inhibitor program and we see a great potential for this novel class of compounds for the treatment of chronic AF."

A. John Camm, Acesion SAB member and Emeritus Professor of Clinical Cardiology, St. George's University of London, said: "With the numbers suffering from Atrial Fibrillation forecast to grow dramatically in the coming years, and with the many safety issues associated with currently available drugs, there is a great unmet need for safer AF treatments that can decrease the risk for patients, but also remove barriers for physicians wanting to keep their patients in sinus rhythm by treating them with an antiarrhythmic drug. This novel mechanism holds the promise to deliver on these aspects."

About the AP30663 IV Phase 2 trial

The trial was a randomised, placebo-controlled, double-blind, multi-national phase 2 trial. The trial enrolled 63 patients with a current AF episode lasting at most seven days but without any limitations on time since initial diagnosis of AF. Patients were allowed to have comorbidities in the form of e.g. heart failure (NYHA I-II), stable ischemic heart disease and hypertension. Patients were randomised to AP30663 3 mg/kg and 5 mg/kg or placebo. The primary endpoint was proportion of patients with AF conversion to sinus rhythm within 90 minutes of infusion start. Patients were followed for 30 days. https://www.clinicaltrials.gov/ct2/show/NCT04571385

About Acesion Pharma

Acesion builds on 20 years of know-how with development of small-molecule SK inhibitors and is the world leader in the field of SK channel inhibition, being the only company able to identify and progress SK channel inhibitors into clinical trials. Acesion is developing a pipeline of SK-channel inhibitors, a target that in the heart is predominantly expressed in the atria. This allows for selective treatment of atrial fibrillation (AF) aiming at improved efficacy and cardiac safety. Acesion's AP30663 IV is a short acting conversion therapy for hospitals that has completed a phase 2 trial proving the value of this first-in-class mechanism in AF and thereby de-risking Acesion's broader SK inhibitor pipeline. Acesion's oral program is designed and engineered using in house knowhow to optimise for, and meet, very high hurdles in both efficacy and particularly safety where existing treatments fall short of patient needs. Acesion Pharma is backed by Novo Holdings A/S, Wellcome Trust, Broadview Ventures and FC Capital.

www.acesionpharma.com

About atrial fibrillation (AF)

AF is the most common type of cardiac arrhythmia mainly affecting the elderly population. Lifetime risk for development of AF is estimated at more than one in three. It is forecast to affect 24 million people in the US and EU by 2030. AF is characterized by chaotic electrical activity in the upper chambers of the heart, the atria, resulting in an irregular and high heart rate. AF is associated with impaired quality of life, increased rate of hospitalization, and a five-fold increased risk of stroke. Increasing evidence suggests that patients with AF also face a higher risk of cognitive dysfunction and dementia.

Atrial Fibrillation is often treated by electrical shock to bring the heart back to its normal rhythm (conversion). This requires general anesthesia in a hospital setting. In addition, many patients are likely to benefit from chronic treatment to prevent AF and maintain normal sinus rhythm. Existing drug therapies for cardioversion or prevention of AF are associated with risk of serious cardiac or other adverse effects, resulting in a great need for safer drugs. Yet, there has been a lack of innovation and development with no new chronic AF drug approved for nearly 20 years. A landmark New England Journal of Medicine published clinical trial (https://doi.org/10.1056/NEJMoa2019422) has shown that sinus rhythm maintenance treatment improves survival and long-term outcomes for AF patients.

SOURCE Acesion Pharma