INOpulse (nitric oxide) / Bellerophon Therap, Baylor BioSci - LARVOL DELTA

Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-blind, Placebo-controlled Trial (ATS 2024) - "There was no demonstrable benefit to inhaled nitric oxide in patients with fibrotic interstitial lung disease on supplemental oxygen. The therapy was safe and well-tolerated while the study affirmed the feasibility of actigraphy as a clinical trial endpoint."

Clinical • Cardiovascular • CNS Disorders • Fibrosis • Hypertension • Infectious Disease • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. (PubMed, Ann Am Thorac Soc) - P3 | "There was no demonstrable benefit to iNO in patients with f-ILD on supplemental oxygen in daily physical activity assessed by actigraphy, a potential novel clinical trial endpoint. Clinical trial registration available at www."

Clinical • Journal • Cardiovascular • Fibrosis • Hypertension • Infectious Disease • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Unleashing the full potential of digital outcome measures in clinical trials: eight questions that need attention. (PubMed, BMC Med) - "The impact of key issues highlighted by the eight questions on a primary analysis of a trial are illustrated through a simulation study based on the 2019 Bellerophon INOPulse trial which had time spent in MVPA as a digital outcome measure. These eight questions present broad areas where methodological guidance is needed to enable wider uptake of digital outcome measures in trials."

Journal • Review

REBUILD: A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension (clinicaltrials.gov) - P3 | N=145 | Terminated | Sponsor: Bellerophon Pulse Technologies | Trial completion date: Sep 2024 ➔ Jun 2023 | Active, not recruiting ➔ Terminated; The trial did not meet its primary endpoint, hence was terminated due to futility.

Trial completion date • Trial termination • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Bellerophon Announces Top-Line Data from Phase 3 REBUILD Clinical Trial of INOpulse for Treatment of Fibrotic Interstitial Lung Disease (GlobeNewswire) - P3 | N=145 | REBUILD (NCT03267108) | Sponsor: Bellerophon Pulse Technologies | "Bellerophon Therapeutics...announced top-line results from its pivotal Phase 3 REBUILD clinical trial evaluating the safety and efficacy of INOpulse® for the treatment of fibrotic Interstitial Lung Disease (fILD)...Key REBUILD clinical trial secondary endpoints and safety outputs assessed over 16 weeks of blinded treatment included: Overall Activity showed 3.51 count/min benefit in favor of iNO45 (p=0.8572). Minute Walk Distance showed 0.19 meter benefit in favor of iNO45 (p=0.9866). Patient reported outcomes (St. George’s Respiratory Questionnaire and UCSD Shortness of Breath) were slightly in favor of placebo, while time to event assessments (Clinical Worsening, Clinical Deterioration and Clinical Improvement) showed little difference and none were statistically significant."

P3 data: top line • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Bellerophon Provides Clinical Program Update and Reports First Quarter 2023 Financial Results (GlobeNewswire) - "REBUILD Phase 3 Study: The Company completed the blinded treatment phase of their pivotal Phase 3 REBUILD trial evaluating the safety and efficacy of INOpulse® for the treatment of patients with fILD and anticipates the availability of top-line results in mid-2023. A total of 145 fILD patients were enrolled and treated with either INOpulse at a dose of iNO45 or placebo. 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 Moderate to Vigorous Physical Activity (MVPA) as measured by actigraphy after 16 weeks of chronic treatment. With a total of 145 patients enrolled, the study is powered >90%, (p-value of 0.01) for the primary endpoint of a change in MVPA measured by actigraphy."

P3 data: top line • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Bellerophon Therapeutics Announces Last Patient Has Completed Blinded Treatment in Phase 3 REBUILD Study for INOpulse in Fibrotic Interstitial Lung Disease (GlobeNewswire) - "Bellerophon Therapeutics...today announced that the last patient has completed blinded treatment in the ongoing Phase 3 REBUILD study of INOpulse®, a proprietary pulsatile nitric oxide delivery system, for the treatment of fibrotic interstitial lung disease (fILD). The Company expects to report top-line results from this study in mid-2023."

P3 data: top line • Trial status • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Long-Term Extension Study of Inhaled Nitric Oxide (iNO) for PAH (clinicaltrials.gov) - P3 | N=22 | Active, not recruiting | Sponsor: Bellerophon Pulse Technologies | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Apr 2023

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Bellerophon Therapeutics Receives IND Clearance from China NMPA to Conduct Phase 3 Clinical Trial in China for INOpulse in Fibrotic Interstitial Lung Disease (GlobeNewswire) - "Bellerophon Therapeutics...announced clearance of its Investigational New Drug (IND) application from the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) to conduct a Phase 3 clinical trial to support the registration of INOpulse® for the treatment of fibrotic interstitial lung disease (fILD) in China. The study will utilize Moderate to Vigorous Physical Activity (MVPA) as the primary endpoint and be conducted in collaboration with Bellerophon’s regional partner, Baylor BioSciences, a life sciences company dedicated to the development and commercialization of innovative medical products for Greater China."

New P3 trial • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

REBUILD: A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension (clinicaltrials.gov) - P3 | N=145 | Active, not recruiting | Sponsor: Bellerophon Pulse Technologies | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Bellerophon Therapeutics Announces Completion of Enrollment in Phase 3 REBUILD Study for INOpulse in Fibrotic Interstitial Lung Disease (GlobeNewswire) - "Bellerophon Therapeutics...today announced that the last patient has been enrolled in the ongoing Phase 3 REBUILD study of INOpulse®, a proprietary pulsatile nitric oxide delivery system, for the treatment of fibrotic interstitial lung disease (fILD). The Company now expects to report pivotal top-line results in mid- 2023."

Enrollment closed • P3 data: top line • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Bellerophon Therapeutics Announces License Agreement for the Commercialization of INOpulse in Greater China with Baylor BioSciences (GlobeNewswire) - "Bellerophon Therapeutics...announced that it has entered into a license agreement for the development and commercialization of INOpulse® with Baylor BioSciences, a life sciences company dedicated to the development and commercialization of innovative medical products for Greater China. Under the terms of the license agreement, Bellerophon will receive a license payment of $6 million, payable within 90 days subject to certain closing conditions set forth in the agreement....Baylor BioSciences will receive exclusive rights to develop and commercialize INOpulse within Greater China for diseases associated with pulmonary hypertension, including the lead indication of fibrotic interstitial lung disease (fILD), as well as PH-Sarcoidosis and PH-COPD."

Licensing / partnership • Chronic Obstructive Pulmonary Disease • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Sarcoidosis

REBUILD: A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension (clinicaltrials.gov) - P3 | N=140 | Recruiting | Sponsor: Bellerophon Pulse Technologies | N=300 ➔ 140

Enrollment change • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

REBUILD: A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Bellerophon Pulse Technologies | Trial completion date: Dec 2023 ➔ Sep 2024 | Trial primary completion date: Dec 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Bellerophon Announces FDA Acceptance of Change to Ongoing Phase 3 REBUILD Study of INOpulse for Treatment of Fibrotic Interstitial Lung Disease (GlobeNewswire) - "Bellerophon Therapeutics...announced today that the U.S. Food and Drug Administration (FDA) has accepted the Company’s proposal to reduce the study size for its ongoing registrational REBUILD Phase 3 trial of INOpulse® for the treatment of fibrotic Interstitial Lung Disease (fILD). The new study size of 140 subjects 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....'With over 100 subjects randomized to date, we expect to complete enrollment in the first quarter of 2023, and anticipate the availability of pivotal top-line data in the third quarter of 2023.'"

Enrollment status • P3 data: top line • Idiopathic Pulmonary Fibrosis

REBUILD: A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension (clinicaltrials.gov) - P3; N=300; Recruiting; Sponsor: Bellerophon Pulse Technologies; Phase classification: P2/3 ➔ P3

Phase classification • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Bellerophon Provides Clinical Program Update and Reports Second Quarter 2022 Financial Results (GlobeNewswire) - "Bellerophon Therapeutics...Fibrotic Interstitial Lung Disease (fILD) REBUILD Phase 3 Study: Enrollment is continuing in Bellerophon’s Phase 3 REBUILD registrational study of INOpulse for the treatment of fILD. The REBUILD study plans to enroll 300 fILD patients who will be treated with either INOpulse at a dose of iNO45 or placebo. The primary endpoint is change in moderate to vigorous physical activity (MVPA). 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.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."

Enrollment status • Idiopathic Pulmonary Fibrosis

A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis or Sarcoidosis (clinicaltrials.gov) - P2 | N=17 | Completed | Sponsor: Bellerophon | Active, not recruiting ➔ Completed | Trial completion date: Mar 2022 ➔ Jun 2022

Trial completion • Trial completion date • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sarcoidosis

A Phase 2 Trial of INOpulse in Patients with Sarcoidosis Associated Pulmonary Hypertension (SAPH) Requiring Supplemental Oxygen (ATS 2022) - "INOpulse was well tolerated and associated with clinically meaningful reductions in mean pulmonary artery pressure and pulmonary vascular resistance. The results support the continued development of iNO as a potential treatment option for patients with sarcoidosis complicated by PH."

Clinical • Late-breaking abstract • P2 data • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sarcoidosis

Expanded Access for Patients With Pulmonary Hypertension Associated With Pulmonary Fibrosis (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: Bellerophon

New trial • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis or Sarcoidosis (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Bellerophon | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2021 ➔ Mar 2022 | Trial primary completion date: Jun 2021 ➔ Sep 2021

Enrollment closed • Trial completion date • Trial primary completion date • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sarcoidosis

A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen. (PubMed, Ann Am Thorac Soc) - P3 | "INOpulse was well tolerated and associated with maintenance of physical activity and improved symptomatology in patients with interstitial lung disease who require supplemental oxygen. Further validation of this beneficial effect warrants further study in a phase 3 trial that is currently underway. Clinical Trial Registration with ClinicalTrials.gov: NCT03267108 Primary Source of Funding: Bellerophon Therapeutics."

Clinical • Journal • P2 data • Fibrosis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

"So why did Nitric oxide fail for Bellerophon therapeutics? @RogerAlvarezDO @fabten" (@DoodyGiuliani11)

"Dr. Alvarez, why did inopulse fail for Covid, but @SanotizeD 's Enovid NO spray seems to work?" (@DoodyGiuliani11)

Novel Coronavirus Disease

Bellerophon Provides Clinical Program Update and Reports Second Quarter 2021 Financial Results (GlobeNewswire) - "Bellerophon Therapeutics, Inc...provided a clinical program update and reported financial results for the second quarter ended June 30, 2021....'We continue to progress our INOpulse® inhaled nitric oxide therapy in multiple areas of significant unmet need,' said Fabian Tenenbaum, Chief Executive Officer of Bellerophon. 'Our ongoing pivotal Phase 3 REBUILD study for fibrotic interstitial lung disease, or fILD, patients at risk of associated pulmonary hypertension is progressing well and continuing to enroll."

Trial status • Idiopathic Pulmonary Fibrosis • Pulmonary Arterial Hypertension • Respiratory Diseases