Bellerophon Therapeutics, Inc. provided a clinical program update. Fibrotic Interstitial Lung Disease (fILD) REBUILD Phase 3 Study: Phase 3 REBUILD registrational study enrollment of INOpulse for the treatment of fILD is approaching completion. The reduced study size is 140 fILD patients who will be treated with either INOpulse at a dose of iNO45 or a placebo.

The new study size does not impact the trial's principal objective or endpoints and maintains power of >90% (p-value < 0.01) for the primary endpoint of Moderate to Vigorous Physical Activity (MVPA) based on the effect size observed in Phase 2. If approved, INOpulse would become the first therapy to treat a broad fILD population that includes patients at low-, intermediate- and high-risk of pulmonary hypertension. Following the evaluation of baseline MVPA characteristics, as measured by actigraphy, compliance to treatment, and review of safety data of randomized subjects in the ongoing Phase 3 REBUILD study, the trial's independent Data Monitoring Committee (DMC) supported reducing the target study size from 300 to 140 subjects. The Phase 3 program builds on positive top-line results from the Company's previously reported Phase 2 studies for INOpulse for the treatment of fILD which showed benefits in multiple cardiopulmonary parameters, including pulmonary vascular resistance and improvement in MVPA.

Pulmonary Hypertension-Sarcoidosis (PH-Sarc) Phase 2 Clinical Study: In December 2021, Bellerophon reported positive top-line data from the completed Phase 2 dose escalation study of INOpulse evaluating the acute hemodynamic benefit of INOpulse via right heart catheterization for the treatment of pulmonary hypertension associated with sarcoidosis (PH-Sarc). PH-Sarc is an unmet medical need with no approved therapies and a median survival of approximately five years after diagnosis. The Phase 2 trial was designed as a proof-of-concept study to determine if iNO could demonstrate hemodynamic benefit in PH-Sarc.

All eight subjects demonstrated decreases in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) across the doses of INOpulse utilized in the study. The dose of iNO45 (45 mcg/kg IBW/hr) resulted in a median drop of 20% (-54% to +22%) in PVR, compared to a median baseline PVR of 329 dyne/cm.sec-5; a reduction of 20% or more in PVR is generally considered to be clinically meaningful. Along with the improvements in PVR, mPAP decreased by a median of 6-10% across the doses of iNO30 to iNO125, compared to a median baseline mPAP of 37.2 mmHg.

No treatment-emergent adverse events (TEAEs) or serious adverse events (TESAEs) occurred during the acute hemodynamic dose escalation phase of the study. Based on the results of the acute dose escalation study, Bellerophon designed and submitted to the FDA a proposed exploratory Phase 2 double-blinded placebo-controlled study to investigate the safety and efficacy of iNO45 dosed chronically for six months in patients with PH-Sarc. Subsequently, the Company received FDA clearance to conduct the study and the Company is currently assessing the next steps for the study.