Inhaled APN01, Potential PAH Therapy, Safe in Healthy Adults

Results of Phase 1 trial will further clinical development of APN01

Patricia Valerio, PhD avatar

by Patricia Valerio, PhD |

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An inhaled form of APN01 (alunacedase alfa), APEIRON Respiratory Therapies (AResT)’s investigational therapy for certain lung diseases, was safe and well-tolerated in healthy people, according to data from a Phase 1 clinical trial.

“In addition to meeting all primary [goals] regarding the safety and tolerability of APN01 via a new route of administration, the observed low systemic [whole-body] concentrations of [the therapy]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,” Romana Gugenberger, PhD, AResT’s chief medical and scientific officer, said in a press release.

“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 [whole-body] side effects,” said Markus Zeitlinger, MD. Zeitlinger is the trial’s principal investigator and head of the department of clinical pharmacology at the Medical University of Vienna, in Austria.

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Gugenberger added that “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.”

Early this year, APN01, which was developed originally by APEIRON Biologics, was out-licensed to AResT, a subsidiary of invIOs, which separated from AIPERON.

It is a lab-made soluble form of the angiotensin-converting enzyme 2 (ACE2), which is known to regulate blood pressure and inflammation, and to be implicated in cardiovascular and lung diseases.

Specifically, ACE2, located at the cell surface, works by suppressing the renin-angiotensin-aldosterone system, thereby promoting blood vessel widening and lowering blood pressure. It also decreases inflammation and protects the heart, kidney, liver, lungs, and vessels from damage.

Previous preclinical studies suggested that ACE2-based and ACE2-activating therapies could promote beneficial effects in PAH.

In addition, ACE2 was found to be the receptor protein that SARS-CoV-2, the virus causing COVID-19, binds to and uses to enter and infect cells.

By mimicking ACE2 in a soluble form, APN01 is expected to bind to the virus in circulation, preventing its interaction with the ACE2 receptor in cells and thereby its entry. It also is expected to reduce organ and blood vessel injury, along with SARS-CoV-2-triggered exacerbated inflammation that is known to cause severe lung damage.

APN01, administered directly into the bloodstream, was tested previously in a placebo-controlled Phase 2 clinical trial (NCT04335136) in people with severe COVID-19. Data showed the therapy was safe and well-tolerated, and appeared to reduce the number of patients who died or required invasive ventilation compared with a placebo.

Current trial results

Now, a Phase 1 trial (NCT05065645) evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple increasing doses of an inhaled form of APN01, administered through a jet nebulizer, against a placebo in 40 healthy adults (ages 18–55).

Pharmacokinetics refers to the therapy’s movement into, through, and out of the body, while pharmacodynamics concerns its effects on the body.

Results showed that APN01 was generally safe and well-tolerated across all tested doses. All reported adverse effects were mild-to-moderate in severity, with no participants withdrawing from the trial.

No dose-dependent or dose-limiting toxicities were observed and no participant developed antibodies against the therapy, which could significantly limit its effectiveness.

“With the current trial of inhaled APN01 and our previous Phase 2 trial using [into-the-vein] administration in COVID-19, we have shown that APN01 is a safe and well tolerated potential treatment approach for a number of respiratory diseases,” said Peter Llewellyn-Davies, invIOs’ CEO.

“We are therefore actively reviewing out-licensing options to drive the further development of APN01, and welcome additional expressions of interest from potential partners,” Llewellyn-Davies added.

All the results from the inhaled APN01 Phase 1 trial are being prepared for publication.

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