Phase 1 data for the investigational inhaled nitric oxide therapy Alx1 demonstrated the treatment was well tolerated with no serious side effects in healthy volunteers.
RT’s Three Key Takeaways:
- Safety and Tolerability: In a Phase 1 study, the inhaled nitric oxide prodrug Alx1 was well tolerated at all dose levels with no dose-limiting toxicities or serious adverse events reported.
- Lack of Respiratory Complications: The data showed no instances of bronchospasm, wheezing, or clinically significant methemoglobinemia, which are historical challenges for inhaled nitric oxide delivery.
- Clinical Potential: The dose-proportional pharmacokinetics support further development of the therapy for muco-obstructive airway diseases such as bronchiectasis and COPD.
Vast Therapeutics announced late-breaking Phase 1 data for its inhaled drug candidate Alx1 at the American Thoracic Society (ATS) 2026 International Conference, according to a news release.
The study demonstrated that Alx1, a first-in-class nitric oxide prodrug designed for targeted delivery to the lungs, was well tolerated without safety concerns across all dose levels evaluated. Researchers observed no dose-limiting toxicities and successfully escalated doses above the calculated human effective dose.
The Phase 1 study evaluated 48 healthy volunteers across single ascending dose and multiple ascending dose cohorts using a nebulized formulation of Alx1. The therapy is designed to release nitric oxide locally in the airways over time to enable anti-inflammatory and antimicrobial activity while minimizing systemic exposure.
“What stood out in the data is what we didn’t see,” said Paul Bruinenberg, MD, MBA, chief medical officer of Vast Therapeutics. “No bronchospasm, no methemoglobinemia, no dose-limiting toxicities, even as we escalated past the calculated human effective dose. Those fundamental challenges have held back inhaled nitric oxide gas for decades.”
Key findings from the study include:
- Alx1 was well tolerated at doses up to 172 mg/day.
- No bronchospasm, wheezing, or meaningful reductions in lung function occurred.
- No clinically significant methemoglobinemia was detected at any dose level.
- Transient decreases in blood pressure were observed, consistent with nitric oxide pharmacology, which returned to baseline within 24 hours.
The pharmacokinetics demonstrated dose-proportional increases in systemic exposure across all dose levels. These results support further clinical development for patients with muco-obstructive airway diseases, including bronchiectasis and COPD, according to the company.
“Nitric oxide’s potential as treatment for airway diseases has been known for a long time,” said Nate Stasko, PhD, chief executive officer of Vast Therapeutics. “The problem has always been getting enough of it, in the right place, at the right time without creating new problems in the process. We believe these data represent a gateway for nitric oxide in respiratory medicine.”
Vast Therapeutics is currently developing the technology to deliver sustained-release nitric oxide to address both inflammatory and microbial drivers of lung disease.
