An Inhaled RNA Drug Aims to Fix Cystic Fibrosis a Step Earlier

Aceso Therapeutics has partnered with Aptar Pharma to develop ACT-101, an inhaled antisense oligonucleotide (ASO) for cystic fibrosis, with an IND submission to the FDA planned for 2027. Aptar’s inhalation development arm, Nanopharm, will lead formulation development and device assessment.

What cystic fibrosis is, briefly

CF is caused by mutations in the CFTR gene, which encodes a channel that moves chloride across cell membranes. When the channel is missing or defective, secretions thicken — producing the chronic lung infections, progressive airway damage and pancreatic insufficiency that define the disease. Roughly 100,000 people worldwide have CF.

The most common mutation by far is F508del, carried on at least one allele by the large majority of patients. It causes the CFTR protein to misfold, so the cell’s quality-control machinery destroys it before it ever reaches the cell surface.

Why “a step earlier” is the whole pitch

The last decade transformed CF care through CFTR modulators — correctors that help misfolded protein traffic to the surface, and potentiators that hold the channel open once it gets there. The triple combination elexacaftor/tezacaftor/ivacaftor changed the trajectory of the disease for most patients.

But every modulator works on protein that has already been made. The cell transcribes the mutant gene, builds a defective protein, and the drug then tries to rescue it downstream.

ACT-101 is described as intervening a step earlier. It uses a patented, first-in-class RNA mechanism targeting post-transcriptional regulation to correct or improve CFTR function, and it is specifically optimized for F508del. Acting at the RNA level means influencing what protein gets produced in the first place, rather than repairing the output.

Who it could help

Modulators have not solved CF for everyone. A minority of patients carry mutations that modulators do not address, some cannot tolerate them, and response varies. An approach working through a different mechanism could reach patients the current class leaves behind, and could in principle be combined with modulators rather than replacing them.

Inhaled delivery adds a second argument. Delivering the drug directly to the airway concentrates it where the lung disease is and limits systemic exposure — relevant for a chronic therapy that patients would take for decades.

Why the device partner matters more than it sounds

This is the part that is easy to skip past. An antisense oligonucleotide is a large, highly charged molecule, and turning one into an inhaled medicine is a serious formulation problem, not a packaging decision. The drug must survive aerosolization, reach the deep lung as particles in the right size range, remain stable in the device over shelf life, and get across airway mucus that is — in CF specifically — abnormally thick.

Nanopharm will handle formulation development and device assessment, and Aptar separately runs a biologics compatibility program studying how complex molecules interact with its pulmonary and nasal delivery platforms. Bringing that in during advanced preclinical work, rather than after a molecule is locked, is the sensible sequence.

“This collaboration marks an important milestone for Aceso and for the continued development of potential new approaches for cystic fibrosis,” said Thomas Tran, Aceso’s CEO. Gemma Budd, general manager of Nanopharm, noted that “cystic fibrosis remains a devastating disease with significant unmet need.”

Antisense has a real track record — and a delivery problem

ASOs are not speculative technology. Short synthetic strands of modified nucleic acid that bind a target RNA and change how it is processed, they underpin approved medicines including nusinersen for spinal muscular atrophy and several drugs for rare metabolic and neuromuscular conditions. The chemistry works.

What limits the class is almost always getting the molecule into the right cells. Nusinersen is injected directly into cerebrospinal fluid. Liver-targeted oligonucleotides succeed because a specific sugar tag routes them efficiently into hepatocytes. Where no such route exists, ASOs tend to accumulate in the wrong tissues at the wrong concentrations. The lung has no equivalent of that liver shortcut, which is why the delivery work Aptar is contributing is not a supporting detail but arguably the central risk in the program.

How early this is

Very. ACT-101 is in advanced preclinical development, and the stated goal is an IND in 2027 to enable first-in-human trials. There is no clinical data, no human safety profile, and no efficacy signal in patients.

The history here also warrants caution. Inhaled nucleic acid therapies for CF have an unhappy track record — inhaled gene therapy and mRNA approaches have repeatedly failed to produce durable clinical benefit, usually because getting enough functional material into enough airway cells proved harder than expected. The delivery barrier that makes the lung an attractive target also makes it a difficult one.

What is different now is that the bar has moved. Any new CF therapy must show benefit on top of highly effective modulators, which means trials in a population that is already doing comparatively well — a harder, slower thing to demonstrate. Preclinical research news, not medical advice.