zelpultide alfa (AT-100) / Airway Therap - LARVOL DELTA

A phase 1b randomized, multicenter, dose determination trial of zelpultide alfa (recombinant human surfactant protein D) in preterm neonates at high risk of developing bronchopulmonary dysplasia. (PubMed, Front Pediatr) - P1 | "Bronchopulmonary dysplasia (BPD) ranks among the most severe long-term complications of prematurity. The incidence of BPD was 32.1% vs. 66.7%, the incidence of BPD or death was 54% and 67%, and time on mechanical ventilation was 17.7 vs. 25.8 days in the zelpultide alfa group compared to the air-sham group, respectively. This study endorses the safety and tolerability of zelpultide alfa up to 6 mg/kg (≤7 days) and reinforces the need for further clinical development of zelpultide alfa as a therapy for preventing BPD.Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04662151?cond=BPD&term=At-100&rank=1, identifier NCT04662151."

Clinical • Journal • P1 data • Bronchopulmonary Dysplasia • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

ZELA: Efficacy and Safety of Zelpultide Alfa in Preterm Neonates at High Risk of Developing Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P2/3 | N=366 | Active, not recruiting | Sponsor: Airway Therapeutics, Inc. | Phase classification: P3 ➔ P2/3 | Trial completion date: Jul 2029 ➔ Feb 2030 | Trial primary completion date: Aug 2027 ➔ Dec 2027

Phase classification • Trial completion date • Trial primary completion date • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

ZELA: Efficacy of Zelpultide Alfa in Preterm Neonates at High Risk of Developing Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P3 | N=316 | Active, not recruiting | Sponsor: Airway Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

ZELA: Efficacy of Zelpultide Alfa in Preterm Neonates At High Risk of Developing Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P3 | N=316 | Recruiting | Sponsor: Airway Therapeutics, Inc.

New P3 trial • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

A Clinical Safety Study of AT-100 (rhSP-D) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: Airway Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Randomized Blinded Phase 1b Study Demonstrates Safety and Tolerability of Zelpultide Alfa (rhSP-D) in Preterm Neonates at High Risk for the Development of Bronchopulmonary Dysplasia (BPD) (ATS 2024) - "This phase 1b study showed that zelpultide alfa is safe and well tolerated. Although the study was not powered for efficacy, results showed a trend to reduction of the incidence of BPD and days on mechanical ventilation in the zelpultide alfa treated group."

Clinical • P1 data • Prematurity • Bronchopulmonary Dysplasia • Cardiovascular • Hypertension • Inflammation • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Clinical Safety Study of AT-100 (rhSP-D) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Airway Therapeutics, Inc. | Phase classification: P1b ➔ P1

Phase classification • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

A Clinical Safety Study of AT-100 (rhSP-D) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P1b | N=36 | Active, not recruiting | Sponsor: Airway Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection or Severed Community Acquired Pneumonia (clinicaltrials.gov) - P1b | N=5 | Terminated | Sponsor: Airway Therapeutics, Inc. | Trial completion date: Jun 2023 ➔ Feb 2023 | Recruiting ➔ Terminated; Termination / study goals reached

Trial completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

A Clinical Safety Study of AT-100 (rhSP-D) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P1b | N=36 | Recruiting | Sponsor: Airway Therapeutics, Inc. | Trial completion date: Mar 2023 ➔ May 2024 | Trial primary completion date: Mar 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection or Severed Community Acquired Pneumonia (clinicaltrials.gov) - P1b | N=9 | Recruiting | Sponsor: Airway Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Jun 2023 | Trial primary completion date: Oct 2022 ➔ May 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Characterization Of Oligomer Formation Of Surfactant Protein-D (Sp-D) Using Af4-Malls. (PubMed, Curr Protein Pept Sci) - "AF4-MALLS technology appears to be a powerful analytical approach to characterize the complex and dynamic interplay among different protein oligomeric species of SP-D in an aqueous solution."

Journal • Infectious Disease • Respiratory Diseases • PROS1

RECOMBINANT HUMAN SURFACTANT PROTEIN D (RHSP-D) REDUCES VIRAL LOAD AND ATTENUATES LUNG INJURY INDUCED BY SARS-COV-2 IN COVID-19 (ESPID 2022) - "Intratracheal administration of rhSP-D at 2&6 mg/kg showed a significant reduction of SARS-CoV-2 titers in lungs 48h post-infection compared to placebo; 96h post-infection, a reduction in viral titers was still observed with administration of 4 mg/kg of rhSP-D. No differences were found in the body weight between experimental groups over time. Using a different delivery route, intranasal rhSP-D at a dose range 2-8 mg/kg attenuated the epithelial injury with cell death, bronchiolitis, alveolitis and inflammation in lungs at day 2 and 7 post-SARS-CoV-2 infection, which was assessed by microscopic analysis of lung histopathology."

Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Otorhinolaryngology • Pediatrics • Pneumonia • Pulmonary Disease • Respiratory Diseases

A Clinical Safety Study of AT-100 (rhSP-D) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P1b | N=36 | Recruiting | Sponsor: Airway Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2022 ➔ Jan 2023 | Trial primary completion date: Dec 2021 ➔ Jan 2023

Enrollment open • Trial completion date • Trial primary completion date • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection (clinicaltrials.gov) - P1b | N=9 | Recruiting | Sponsor: Airway Therapeutics, Inc. | Trial completion date: Mar 2022 ➔ Dec 2022 | Trial primary completion date: Jan 2022 ➔ Oct 2022

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection (clinicaltrials.gov) - P1b; N=9; Recruiting; Sponsor: Airway Therapeutics, Inc.; Not yet recruiting ➔ Recruiting; Trial completion date: Jul 2021 ➔ Mar 2022; Initiation date: Jan 2021 ➔ Aug 2021; Trial primary completion date: Jun 2021 ➔ Jan 2022

Clinical • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Full-Length Recombinant hSP-D Binds and Inhibits SARS-CoV-2. (PubMed, Biomolecules) - "Therefore, SP-D recognizes and binds to the spike-(S)-protein of SARS-CoV-2 in vitro, initiates the aggregation, and inhibits viral replication in cells. Combined with the low levels of SP-D observed in COVID-19 patients, these results suggest that SP-D is important in the immune response to SARS-CoV-2 and that rhSP-D supplementation has the potential to be a novel class of anti-viral that will target SARS-CoV-2 infection."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem. (PubMed, Respir Res) - "Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD."

Journal • Review • Bronchopulmonary Dysplasia • Immunology • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Rare Diseases • Respiratory Diseases • TLR4

Airway Therapeutics Announces FDA Acceptance of IND for AT-100's Second Indication in Severe COVID-19 Patients (PRNewswire) - "Initiating Phase 1b clinical trial with initial results expected 3Q2021....The U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application to develop AT-100 (rhSP-D) as a treatment for COVID-19. Airway is leveraging the FDA's Coronavirus Treatment Acceleration Program (CTAP) that is aimed at evaluating new treatment options for COVID-19. Airway will initiate a Phase 1b clinical trial to confirm the feasibility of intratracheal administrations of AT-100 and its beneficial safety and tolerability profile....The Phase 1b clinical trial will begin later this month."

IND • P1 data • Trial initiation date • Infectious Disease • Novel Coronavirus Disease

Phase 1b Study on AT-100 Intervention (rhSP-D) in Preterm Neonates at High Risk for Development of Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P1b; N=36; Not yet recruiting; Sponsor: Airway Therapeutics, Inc.; Phase classification: P1b/2 ➔ P1b

Phase classification • Bronchopulmonary Dysplasia • Respiratory Diseases

Phase 1b Study on AT-100 Intervention (rhSP-D) in Preterm Neonates at High Risk for Development of Bronchopulmonary Dysplasia (BPD) (clinicaltrials.gov) - P1b; N=36; Not yet recruiting; Sponsor: Airway Therapeutics, Inc.

New P1 trial • Bronchopulmonary Dysplasia • Respiratory Diseases

A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection (clinicaltrials.gov) - P1b; N=9; Not yet recruiting; Sponsor: Airway Therapeutics, Inc.

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

Airway Therapeutics and Celonic Group collaborate to produce AT-100 as promising new candidate for coronavirus (PRNewswire) - "Airway Therapeutics, Inc....and Celonic Group...today announced a collaboration to produce the novel human recombinant protein AT-100 (rhSP-D) as a therapeutic candidate against COVID-19. Based on the agreement, Celonic will be responsible for process optimization and GMP manufacturing of AT-100 for clinical study. Production of AT-100 is expected to begin in June 2020."

Licensing / partnership • Infectious Disease • Novel Coronavirus Disease

Airway Therapeutics announces filing with NIH to evaluate AT-100 as a therapy for novel coronavirus (PRNewswire) - “Airway Therapeutics…announced a filing with…National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), to evaluate AT-100 (rhSP-D) as a therapeutic for the novel coronavirus (COVID-19)….The COVID-19 outbreak has illuminated the urgency to identify and explore new therapies for patients in need….and advance AT-100 as a potential therapeutic option.”

Clinical