PhaseBio Pharmaceuticals said today it won a $2.8 million Fast Track Small Business Innovation Research (SBIR) grant from the NIH toward clinical development of its lead candidate PB1046 for pulmonary arterial hypertension (PAH).

PB1046 is a first-in-class, sustained-release vasoactive intestinal peptide (VIP) analog already under study in an ongoing Phase I clinical trial (NCT03315507).

The trial, PB1046-PT-CL-000, is an open-label, dose-titration study designed to assess the safety, tolerability, and hemodynamic effects of individually dose-titrated PB1046 injected weekly over 8 weeks in adults with PAH who have a permanently implanted hemodynamic monitor (CardioMEMS™ HF System) in the distal pulmonary artery.

The Phase I portion of the grant will fund the ongoing exploratory trial, while the Phase II portion will support a larger, Phase II trial in PAH set to launch by mid 2018, PhaseBio said.

PB1046 is a once-weekly VIP receptor agonist designed to target VPAC receptors in the cardiovascular, pulmonary, and immune systems. PhaseBio reasons that VIP-based therapies are likely to provide benefit in PAH, cardiomyopathy, and other cardiovascular diseases, since VIP is known to have vasodilatory, inotropic, lusitropic, and antifibrotic effects, and several cardiopulmonary disorders are associated with alterations in levels of VIP or its receptors, VPAC1 and VPAC2.

Along with VIP, those receptors are believed to be a critical factor in the development and progression of PAH, according to the company.

“Consequently, VIP-based therapies, like PB1046, may provide compelling new treatment options that could reverse disease progression and improve long-term patient outcomes,” PhaseBio CEO Jonathan P. Mow said in a statement. “This grant award validates our therapeutic approach and PhaseBio’s position as an emerging player in the development of innovative therapies for rare diseases.”

PB1046 consists of an analog of VIP fused to PhaseBio’s elastin-like polypeptide (ELP) biopolymer. The drug is designed to overcome the poor in vivo stability and bioavailability of the native VIP peptide, as well as bind to the VPAC2 receptor to minimize potential gastrointestinal side effects.

According to PhaseBio, PB1046 showed a prolonged, dose-dependent effect on blood pressure in a Phase I study in patients with essential hypertension, as well as “clear efficacy” in animal models of heart failure, PAH, and Duchenne muscular dystrophy-related cardiomyopathy.

In addition to the exploratory trial, PB1046 is also under study in a Phase IIa multiple ascending-dose study in subjects with heart failure (NCT02808585). That study was active but not recruiting patients as of November 6, according to ClinicalTrials.gov.

The FDA has granted PB1046 orphan drug designation for the treatment of PAH (WHO Group 1 PH) as well as cardiomyopathy associated with dystrophinopathies.

“Recent advancements in the treatment of PAH have improved patient symptoms and exercise capacity, but are not curative, and long-term disease prognosis remains poor, leaving the door open for innovative new therapeutic options like PB1046,” added PhaseBio CMO John Lee, M.D., Ph.D., principal investigator for the SBIR grant.








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