APEIRON Respiratory Therapies Announces Positive Results From Phase I Trial of Inhaled APN01

APEIRON Respiratory Therapies GmbH recently announced positive final results from a Phase 1 clinical trial of inhaled APN01 (alunacedase alfa), a soluble recombinant version of the SARS-CoV-2 cell entry receptor ACE2.

The study met all primary and secondary endpoints, with all results indicating that the inhalation of APN01 at all dosage levels used in the trial is safe and well tolerated. In the study, no dose-limiting toxicities were observed. No serious adverse events were reported, and no patients withdrew from the trial.

Professor Markus Zeitlinger, Head of the Department of Clinical Pharmacology at the Medical University of Vienna and Principal Investigator for the study, said “I am very happy that our team was able to contribute to the development of this potential treatment for patients suffering from different forms of severe respiratory disease. The inhaled route of administration may enable the achievement of very high concentrations at the site of action, without compromising patient safety due to systemic side effects. We were able to confirm a good tolerability profile from a clinical perspective.”

Dr. Romana Gugenberger, Chief Medical and Scientific Officer of AResT, added “The results of this study allow further clinical development of novel inhaled APN01 and expand its potential as a treatment for a range of respiratory diseases. In addition to meeting all primary endpoints regarding the safety and tolerability of APN01 via a new route of administration, the observed low systemic concentrations of ACE2 indicate that inhaled APN01 may be an effective treatment for chronic conditions such as pulmonary arterial hypertension as well as acute indications like COVID-19.”

In a completed double-blind, placebo-controlled Phase 2 trial, intravenously administered APN01 showed potential clinical benefit against COVID-19. The drug candidate also may have potential in other respiratory diseases such as acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH).

APN01 was previously developed by APEIRON Biologics AG, a privately held biotech company based in Vienna, Austria, and out-licensed to AResT, which was demerged from APEIRON Biologics AG in 1H 2022 to continue the development of APN01. AResT is a 100% subsidiary of invIOs GmbH (invIOs), which was also demerged from APEIRON Biologics AG in 1H 2022 to focus on the discovery and development of innovative cancer immunotherapies.

Peter Llewellyn-Davies, CEO of invIOs, said “We are pleased with the results of this study, as it opens numerous additional avenues for the further development of APN01. With the current trial of inhaled APN01 and our previous Phase 2 trial using intravenous administration in COVID-19, we have shown that APN01 is a safe and well tolerated potential treatment approach for a number of respiratory diseases. We are therefore actively reviewing out-licensing options to drive the further development of APN01, and welcome additional expressions of interest from potential partners.”

The double-blind, placebo-controlled, dose-escalation study was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of inhaled APN01. The trial enrolled 40 healthy adult subjects aged 18-55 years. The primary objective of the trial was to evaluate the safety and tolerability of single ascending doses (SADs) and multiple ascending doses (MADs) of inhaled APN01 administered via a jet nebulizer. Secondary objectives included evaluation of the maximum tolerated dose and investigation of the potential immunogenicity of inhaled APN01.

Inhaled APN01 Phase 1 trial final results

Safety

• Treatment was safe and well tolerated. All adverse events were mild to moderate with none above Grade 2.
• No dose-dependent toxicities were observed.

Maximum tolerated dose

• No dose-limiting toxicities were observed. Accordingly, the maximum tolerated dose as defined by the study was the highest dose level in the MAD cohort.

Immunogenicity

• No anti-APN01 antibodies were detected in any of the subjects.

A paper describing the trial and its full results is in preparation.

APN01 is a soluble recombinant human Angiotensin Converting Enzyme 2 (rhACE2). Several studies have shown that human ACE2 is a key enzyme regulator of the Renin Angiotensin Aldosterone System (RAAS), a hormone system involved in regulation of blood pressure, lung disorders, diabetic kidney disease, inflammation, or cardiovascular diseases. ACE2, a homologue of ACE, has vasodilative and biological effects on vascular remodeling exercised through hydrolysis of Ang‐II to Ang(1‐7). Ang(1‐7) counteracts Ang‐I effects and thereby reduces blood pressure, diminishes inflammation, and protects multiple organs such as the heart, kidney, liver, lung and vasculature from damage.

In addition, APN01 mimics ACE2, a receptor identified as the critical cellular entry receptor for the SARS-CoV-2 virus and therefore plays a crucial role in combating COVID-19. In addition to blocking the access of SARS-CoV-2 to its cell membrane-bound entry gate, the enzyme function of APN01, engineered into the same drug, potentially leads to reduction of organ injuries in COVID-19. Due to the unique therapeutic approach of using the soluble form of the SARS-CoV-2 entry receptor ACE2, APN01 is inherently resilient to viral escape, and thus an optimal drug candidate for novel variants of concern, as already shown for many variants of concern in clinical studies. In a double-blind, randomized, placebo-controlled, interventional Phase 2 trial evaluating intravenously administered APN01 in patients with severe COVID-19, APN01 appeared to reduce the number of deaths and the number of patients requiring invasive ventilation and was shown to be well tolerated with a favorable safety profile.

AResT was spun out of APEIRON Biologics AG at the beginning of 2022 to continue the development of APN01. AResT is a 100% subsidiary of invIOs GmbH, which focuses on the development of the immuno-oncology assets of APEIRON Biologics. More information on the demerger of AResT and invIOs from APEIRON Biologics AG can be found on the invIOs website here.

invIOs is a privately held biotech company based in Vienna, Austria, focusing on the discovery and development of innovative cancer immunotherapies.

EPiC, invIOs’s proprietary cell therapy platform for intracellularly modifying gene expression, enables rapid treatment of patients in an out-patient setting using their own fresh immune cells. Once clinically validated, this novel concept will allow access to and treatment for indications not previously addressable by immunotherapy.

The first EPiC-based candidate, APN401, is currently being evaluated in a clinical Phase 1b trial in patients with advanced solid tumors. Two further projects – a second EPiC-based candidate and a novel small molecule – are currently in pre-clinical development. For more information, visit www.invios.com.