Tiakis ready to advance tiprelestat to Phase 2 trial for PAH
Experimental therapy aimed at modifying disease progression
Tiakis Biotech is set to advance its experimental therapy tiprelestat into a Phase 2 clinical trial for pulmonary arterial hypertension (PAH), after successfully finalizing the data package required for regulatory review.
The planned study, dubbed ATHENA, will be led by Stanford University and will enroll about 90 patients with a diagnosis of PAH. Participants will be randomly assigned to receive either tiprelestat or a placebo in addition to their standard PAH treatments for 24 weeks, or about six months. The therapy aims to address underlying biological processes that contribute to the development and progression of PAH.
Stanford has been awarded a grant from the U.S. National Institutes of Health to conduct the trial, which is expected to begin in mid-2026 pending final clearance from the U.S. Food and Drug Administration.
The agency issued a positive scientific opinion on the study design earlier this year.
“We are excited to have finalized a robust data package for the Phase II ATHENA trial of Tiprelestat in PAH,” Martin Voss, CEO of Tiakis, said in a company press release. “Pulmonary arterial hypertension remains an area of urgent unmet need, with current registry data showing a 5-year survival rate of only 57% of diagnosed PAH patients. We believe Tiprelestat holds significant promise as a potential disease-modifying therapy.”
Tiprelestat is a lab-made version of elafin
PAH is a condition in which the pulmonary arteries, the vessels that carry blood from the heart to the lungs, gradually become thickened, stiffened, and narrowed. As blood flow through the lungs becomes restricted, pressure rises within these arteries, forcing the right side of the heart to work harder to pump blood forward. Over time, this strain can lead to right-heart failure.
Among the underlying causes of PAH are mutations in the BMPR2 gene, which result in a deficiency of the BMPR2 protein that normally controls the growth of blood vessel cells. As a result, these cells proliferate unchecked, causing arterial walls to thicken and narrow.
Tiprelestat is a lab-made version of elafin, a naturally occurring protein that protects tissues from inflammation-driven damage. It works by blocking neutrophil elastase, an enzyme present at unusually high levels in people with PAH, as well as another protein called proteinase 3. By targeting them, tiprelestat seeks to reduce inflammation and slow, or potentially reverse, the vascular remodeling (structural alterations in blood vessels) that drives PAH progression.
Earlier clinical studies showed consistently favorable safety profile
The data package incorporates safety findings from five earlier clinical studies of tiprelestat involving more than 100 individuals, all of which showed a consistently favorable safety profile.
It also includes results from a toxicology study in rats, in which animals received daily subcutaneous (under-the-skin) injections of tiprelestat at 5 mg/kg or 20 mg/kg, or a placebo, for 180 days (about six months).
According to Tiakis, no side effects were observed at any dose. The company noted that the highest dose corresponds to a human-equivalent exposure that offers roughly a 20-fold safety margin over the dose intended for clinical use in people with PAH.
ATHENA’s main goal will be to evaluate changes in pulmonary vascular resistance, a key measure of the force the right side of the heart must generate to push blood through the lungs. Changes in patients’ functional capacity, assessed through the six-minute walk distance test, will be assessed as a secondary measure.
Tiprelestat has been granted orphan drug designation for PAH in both the U.S. and the European Union. This status is granted to treatments targeting rare diseases and offers benefits such as regulatory support, fee reductions, and, if the therapy is ultimately approved, several years of market exclusivity.
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