Stanford University has secured a double-digit million dollar grant from the National Institutes of Health (NIH) to advance a Phase II clinical trial of Tiprelestat, an investigational therapy for pulmonary arterial hypertension (PAH) developed by German biopharmaceutical company tiakis Biotech AG. The grant, awarded by the National Heart Lung and Blood Institute's Lung Division, represents a significant milestone for a potential disease-modifying treatment targeting this fatal rare disease.
The U.S. FDA issued positive scientific advice on the planned trial design in early 2025, with the first patients expected to begin treatment at Stanford University in mid-2026. The NIH award number UG3HL180990 will fund the comprehensive Phase II study, while tiakis Biotech will provide clinical trial materials at its own expense.
Addressing Critical Unmet Medical Need
PAH represents a devastating condition with limited treatment options and poor long-term outcomes. Current registry data indicates that the five-year survival rate for PAH patients is only 57%, highlighting the urgent need for innovative therapeutic approaches. Existing treatments focus on restoring the balance between vasoconstriction and vasodilation by targeting endothelin, nitric oxide, and prostacyclin pathways, but fail to address the underlying disease mechanisms.
"There is an urgent medical need for new therapies specifically targeting pulmonary vascular remodeling and inflammation," according to the source materials describing the current treatment landscape.
Novel Mechanism of Action
Tiprelestat distinguishes itself from current PAH therapies through its unique mechanism of action that addresses fundamental pathological processes underlying the disease. Professor Marlene Rabinovitch, the Dwight and Vera Dunlevie Professor of Pediatric Cardiology and Director of the Basic Science and Engineering Initiative of the Children's Heart Center at Stanford University, explained that "Tiprelestat holds the promise of a disease-modifying therapy because of its unique mechanism of action which addresses major pathological processes in PAH, specifically inflammation and BMPR2 deficiency."
The investigational therapy has been developed as a disease-modifying treatment that can potentially address underlying inflammation and reverse the vascular remodeling characteristic of this debilitating condition. This approach represents a significant departure from symptom management toward targeting the root causes of PAH progression.
Strong Safety Profile and Regulatory Recognition
Tiprelestat has demonstrated an excellent safety profile across five clinical trials involving more than 100 subjects, providing a solid foundation for the upcoming Phase II study. The therapy has received orphan designation for PAH in both the United States and Europe, recognizing its potential to address this rare disease with significant unmet medical need.
Professor Roham Zamanian, Director of the Adult Pulmonary Hypertension Program at Stanford University and Principal Investigator of the trial, emphasized the significance of the NIH recognition: "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."
Collaborative Research Framework
The Phase II trial represents a continuation of the long-standing collaboration between Stanford University and tiakis Biotech AG. The study will also involve Dr. Cathie Spino at the SABER unit of the University of Michigan, who leads the companion award for the Data Coordinating Center.
Martin Voss, CEO of tiakis Biotech AG, highlighted the collaborative nature of the research: "This award recognizes Tiprelestat's potential and pioneering approach by scientific and clinical experts at this well-respected institute."
Clinical Development Timeline
With FDA scientific advice already secured and the NIH grant in place, the Phase II trial is positioned to begin patient enrollment in mid-2026. Professor Rabinovitch noted that "data from the planned U.S. Phase II trial are expected to confirm this hypothesis" regarding Tiprelestat's disease-modifying potential.
The clinical-stage biopharmaceutical company tiakis Biotech AG, based in Kiel, Germany, specializes in developing anti-inflammatory treatments with a primary focus on pulmonary arterial hypertension and other life-threatening pulmonary and cardiovascular diseases.
