17 July 2020 - - US-based biopharmaceutical company PhaseBio Pharmaceuticals, Inc. (NASDAQ: PHAS) has dosed the first patient in VANGARD, a potentially pivotal Phase 2 clinical trial to evaluate PB1046 as a treatment for hospitalized COVID-19 patients who are at high risk for rapid clinical deterioration and acute respiratory distress syndrome, the company said.

PB1046 is a novel, once-weekly, subcutaneously-injected VIP receptor agonist that targets VPAC receptors in the cardiovascular, pulmonary and immune systems. VIP is a neurohormone known to have anti-inflammatory, antifibrotic and potent bronchodilatory and immunomodulatory effects in the respiratory system.

Specifically, VIP has been shown to regulate proinflammatory cytokines including TNF-α, IFN-γ, IL-12, IL-17A and IL-6. In animal models, treatment with VIP peptide prevented acute lung injury and inhibited cytokine-mediated inflammatory responses that are characteristic of ARDS.

The VANGARD trial (VIP ANalogue, in hospitalized COVID-19 patients at hiGh risk for rapid clinical deterioration and ARDS) is a multi-center, randomized, double-blind, parallel group clinical trial that is assessing the efficacy and safety of once-weekly subcutaneous injections of PB1046 in hospitalized COVID-19 patients at high risk for rapid clinical deterioration and ARDS.

Approximately 210 patients will be targeted to be enrolled at approximately 20 sites nationwide. The primary endpoint in the trial measures days alive and free of respiratory failure.

As the COVID-19 pandemic unfolded around the world, PhaseBio moved rapidly to develop a trial protocol and submit an IND application to the FDA to evaluate the potential of PB1046 to help COVID-19 patients at high risk of progressing to ARDS.

PhaseBio received FDA clearance in May to initiate the VANGARD trial and, subject to the pace of enrollment and any further impacts from the COVID-19 pandemic itself, the company is targeting to report results late in the fourth quarter of 2020.

Based on feedback from the FDA, PhaseBio believes that positive, clearly interpretable and clinically meaningful results from this trial may enable PhaseBio to submit a Biologics License Application.

More information about the VANGARD phase 2 trial is available at ClinicalTrials.gov, using the identifier NCT04433546.

PB1046, a novel, subcutaneously-injected vasoactive intestinal peptide analogue, is a recombinant fusion protein composed of VIP and PhaseBio's proprietary elastin-like polypeptide biopolymer.

Based on the pharmacokinetic profile of PB1046 observed in clinical trials, the fusion of VIP to ELP results in both a prolonged absorption profile and a longer circulating half-life, enabling once-weekly dosing.

PB1046 is in Phase 2 development for the treatment of pulmonary arterial hypertension and in a Phase 2 clinical trial for the treatment of hospitalized COVID-19 patients at high risk for rapid clinical deterioration and ARDS, which the company refers to as the VANGARD trial.

PhaseBio expects to report initial data from the VANGARD trial in the fourth quarter of 2020, while results from the Phase 2b trial in PAH are expected to be reported in 2021.

To date, PB1046 has been administered to more than 70 patients with hypertension or a history of cardiovascular disease in three Phase 1/2 clinical trials conducted in the United States.

The FDA has granted PB1046 orphan drug designation for the treatment of pulmonary arterial hypertension (WHO Group 1 Pulmonary Hypertension) and cardiomyopathy associated with dystrophinopathies.

PhaseBio Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for cardiopulmonary diseases.

The company's pipeline includes: bentracimab (PB2452), a novel reversal agent for the antiplatelet therapy ticagrelor; PB1046, a once-weekly vasoactive intestinal peptide receptor agonist for the treatment of pulmonary arterial hypertension and hospitalised COVID-19 patients at high risk for rapid clinical deterioration and ARDS; and PB6440, an oral agent for the treatment of resistant hypertension.

PhaseBio's proprietary elastin-like polypeptide technology platform enables the development of therapies with potential for less-frequent dosing and improved pharmacokinetics, including PB1046, and drives both internal and partnership drug-development opportunities.

PhaseBio is located in Malvern, PA, and San Diego, CA.