Stanford awarded NIH grant for PAH treatment clinical trial
Phase 2 ATHENA trial to test tiprelestat in 90 PAH patients
Stanford University has been awarded a grant from the U.S. National Institutes of Health (NIH) to begin a Phase 2 clinical trial of pulmonary arterial hypertension (PAH) treatment tiprelestat, the treatment’s developer announced.
Tiakis Biotech said tiprelestat was found to be safe in earlier clinical trials involving more than 100 participants.
The new trial, ATHENA, plans to enroll 90 patients diagnosed with PAH. The U.S. Food and Drug Administration (FDA) provided feedback on its design, and the first patients are expected to begin treatment in mid-2026.
“This award recognizes tiprelestat’s potential and pioneering approach by scientific and clinical experts at this well-respected institute,” Martin Voss, CEO of Tiakis, said in a company press release. Voss congratulated the researchers on receiving the award.
PAH occurs when the pulmonary arteries, which carry blood from the heart to the lungs, narrow. This makes it difficult for blood to flow through the lungs, causing high blood pressure in these blood vessels and in the right side of the heart.
‘Transformative’ treatment reverses PAH changes in rats
Causes of PAH include mutations in the BMPR2 gene, which codes for a protein that controls how much blood vessel cells grow. These genetic mutations reduce the amount of this protein in cells or prevent it from properly relaying signals. As a result, cells — such as those around blood vessels in the lungs — overgrow and cause blood vessels to narrow.
Tiprelestat is a lab-made version of elafin, a protein that reduces inflammation by blocking neutrophil elastase — which is present in PAH at higher levels than in healthy people — and another protein called proteinase 3. In model rats, lab-made elafin reversed changes associated with PAH, including enlargement of the heart and narrowing of the pulmonary artery.
“The NIH grant is an outstanding validation and recognition of tiprelestat’s robust science and its potential to deliver a truly transformative therapy for PAH patients,” said Roham Zamanian, MD, director of Stanford’s Adult Pulmonary Hypertension Program and principal investigator of the planned trial.
The clinical trial will randomly assign patients to receive either tiprelestat or a placebo in addition to their standard PAH treatments. Its main goal is to monitor changes in pulmonary vascular resistance, a measure of the resistance that must be overcome for blood to flow through blood vessels in the lungs.
As a secondary goal, the researchers will measure the six-minute walk distance, or how far patients can walk in six minutes. ATHENA will also include a four-week withdrawal period to understand whether tiprelestat can modify the course of the disease.
“Tiprelestat holds the promise of a disease-modifying therapy because of its unique mechanism of action which addresses major [disease-related] processes in PAH, specifically inflammation and BMPR2 deficiency,” said Marlene Rabinovitch, MD, a Stanford professor who is also principal investigator for ATHENA. “Data from the planned U.S. Phase II trial are expected to confirm this hypothesis.”
Tiprelestat has been granted orphan drug designation for PAH in both the U.S. and the European Union. This designation is given to treatments for rare diseases, and comes with benefits including years of market exclusivity if the therapy is ultimately approved.
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