The National Institutes of Health (NIH) awarded a $2.8 million Fast Track Small Business Innovation Research (SBIR) grant to PhaseBio Pharmaceuticals to advance the clinical development of PB1046, the first sustained-release analogue of the natural vasoactive intestinal peptide (VIP), in patients with pulmonary arterial hypertension (PAH).
In the first stage, the grant will support an ongoing exploratory Phase 1 clinical trial investigating the safety, tolerability, and hemodynamic effects of PB1046 in adults with PAH using a permanently implanted hemodynamic monitor. The open-label study (NCT03315507) is currently recruiting participants.
In the second stage, the grant will support a larger Phase 2 clinical trial in PAH. PhaseBio Pharmaceuticals plans to begin enrollment in mid-2018.
PB1046 is a VIP receptor agonist, meaning that it mimics the action of VIP in activating receptor proteins, called VPAC, that are found in cells from the pulmonary, cardiovascular, and immune systems. The therapy is delivered in a subcutaneous injection once a week.
Previous studies showed that VIP has several effects beneficial for PAH and other cardiovascular diseases, including vasodilatory and antifibrotic activity.
“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,” John Lee, MD and PhD, chief medical officer of PhaseBio and the grant’s principal investigator, said in a press release.
“PB1046’s novel mechanism of action targets VPAC receptors, which, along with VIP, are believed to be a critical factor in the development and progression of PAH. Consequently, VIP-based therapies, like PB1046, may provide compelling new treatment options that could reverse disease progression and improve long-term patient outcomes,” said Jonathan P. Mow, CEO of PhaseBio.
PhaseBio developed PB1046 fused to their proprietary elastin-like polypeptide (ELP) biopolymer, which improves the therapy’s stability in the body and provides a binding preference to the VPAC2 receptor to minimize potential gastrointestinal side effects.
PB1046 was well-tolerated and showed a dose-dependent effect in hypertension patients in a Phase 1 clinical trial. Preclinical studies with animal models of PAH, heart failure, and Duchenne muscular dystrophy-related cardiomyopathy also support the therapy’s efficacy.
Currently, PhaseBio is evaluating multiple ascending doses of PB1046 in a Phase 2a trial in patients with heart failure.
“This grant award validates our therapeutic approach and PhaseBio’s position as an emerging player in the development of innovative therapies for rare diseases,” Mow said.
The U.S. Food and Drug Administration granted PB1046 orphan drug status for the treatment of PAH and cardiomyopathy associated with muscle weakness (dystrophinopathies).