Zelpultide alfa - Airway Therapeutics
Alternative Names: AT-100; rhSP-DLatest Information Update: 12 Jun 2023
At a glance
- Originator Airway Therapeutics
- Class Anti-infectives; Anti-inflammatories; Antivirals; Recombinant proteins
- Mechanism of Action Cell membrane permeability enhancers; Protein replacements; Virus replication inhibitors
-
Orphan Drug Status
Yes - Bronchopulmonary dysplasia
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Phase I Bronchopulmonary dysplasia; COVID 2019 infections
- Preclinical Influenza virus infections; Respiratory syncytial virus infections
- Research Inflammation; Respiration disorders
Most Recent Events
- 05 Jun 2023 Airway Therapeutics completes enrolment in its phase Ib trial for Bronchopulmonary dysplasia in USA and Spain
- 05 Jun 2023 Airway Therapeutics plans a phase III trial for Bronchopulmonary dysplasia in North America and Europe by the end of 2023
- 27 Feb 2023 Early research in Inflammation in USA (unspecified route) (Airway Therapeutics pipeline, February 2023)
Development Overview
Introduction
Zelpultide alfa (formerly AT 100) is a recombinant version of human surfactant protein D (rhSP-D), being developed by Airway Therapeutics, for the prevention of bronchopulmonary dysplasia (BPD) in very premature infants and for the treatment of COVID-2019 infections. Zelpultide alfa has anti-inflammatory and anti-infective properties and hence it can modulate immune responses across a breadth of respiratory diseases inside and outside the lung. Zelpultide alfa has potential to inhibit SARS-CoV-2 replication and promote viral elimination. Clinical development in COVID-2019 infections and bronchopulmonary dysplasia is ongoing in the US and Spain. Preclinical development in influenza and respiratory syncytial virus infections, and early research in inflammation and other respiratory disorders, is underway in US.
Airway Therapeutics intends to develop rhSP-D, in combination with an inhaled surfactant, for the treatment of cystic fibrosis, in the future. Airway Therapeutics expects that the surfactant-rhSP-D combination could be used for the prevention and treatment of neonatal respiratory distress syndrome (nRDS) as well as for the prevention of BPD.
Airway Therapeutics is using Glycotope’s proprietary GlycoExpress® cell line technology to produce recombinant human surfactant protein D. The Glycotope cell line is designed to optimise the manufacturing and give high-yield production of zelpultide alfa, with fast production cycles.
Company Agreements
In May 2020, Airway Therapeutics entered into a manufacturing agreement with Celonic Group to produce human recombinant protein AT 100 (rhSP-D) as a therapeutic candidate against COVID-19. As pert the agreement terms, Celonic will be responsible for process optimisation and GMP manufacturing of AT 100 for clinical study. [1]
In September 2017, Airway Therapeutics entered into an exclusive licensing agreement with Glycotope. Under the terms of the agreement, Airway received worldwide commercial rights to use Glycotope's proprietary cell line technology, GlycoExpress®, to produce recombinant human surfactant protein D (rhSP-D, AT 100). The Glycotope cell lines will be used for high-yield production of recombinant human surfactant protein D, to provide human glycosylation patterns on the final protein product, and will serve as the basis for the production of the protein for human use. [2]
Airway Therapeutics was formed in June 2011 to develop newer surfactant products based on the research conducted by at Cincinnati Children's Hospital Medical Center. CincyTech and Cincinnati Children's Tomorrow Fund have each invested $US250 000 in the company. The investments are part of a projected $US1.2 million seed-stage funding round led by CincyTech [3] .
Key Development Milestones
In April 2021, Airway Therapeutics announced that they are leveraging US FDA’s Coronavirus Treatment Acceleration Program (CTAP) for the development of zelpultide alfa, for the treatment of COVID-2019 infections [4] .
In September 2021, Airway Therapeutics initiated a phase Ib trial, a dose-determined study evaluating the safety and tolerability profile of intervention with AT 100 (rhSP-D) in preterm neonates at high risk for the development of bronchopulmonary dysplasia (BPD) (NCT04662151; AT-100/001). The randomised, open-label, dual-armed trial intends to enroll 36 participants in the US and Spain. The company dosed its first patient in the trial in October 2022 in Spain [5] [6] [7] . In April 2023, the company announced completion of the dose escalation portion of the trial [8] . In June 2023, Airway Therapeutics successfully completed enrollment in the phase Ib trial of zelpultide alfa for preventive use in very preterm infants at risk for bronchopulmonary dysplasia (BPD) [9] .
In February 2023, Airway Therapeutics terminated a phase Ib trial that designed to evaluate the safety, tolerability and feasibility of zelpultide alfa in patients receiving invasive mechanical ventilation with severe COVID-19 infection, due to study goals reached (AT-100/002; NCT04659122). The non-randomised, open-label trial was initiated in January 2021 and enrolled five patients in the US. In August 2021, first patient in the trial was dosed [10] [11] . In April 2021, Airway Therapeutics announced that, the US FDA has accepted an Investigational New Drug (IND) application for zelpultide alfa to conduct a phase Ib trial for the treatment of COVID-2019 infections [12] . Earlier, in March 2021, Airway Therapeutics, filed an IND application with the US FDA for zelpultide alfa for treatment of COVID-2019 infections [13] .
In March 2021, Airway Therapeutics, reported the acceptance of Investigational New Drug (IND) application by the US FDA of zelpultide alfa for prevention of bronchopulmonary dysplasia (BPD) in very preterm infants [13] .
Prior May 2020, Airway Therapeutics filed a pre-IND submission with the US FDA for zelpultide alfa for the prevention of bronchopulmonary dysplasia (BPD) in very preterm infants [1] .
In March 2020, Airway Therapeutics announced filling with the Respiratory Diseases Branch of the National Institutes of Health (NIH) to evaluate zelpultide alfa, for the treatment of COVID-19 infection [14] .
In March 2017, Airway Therapeutics announced its intention to file an investigational new drug application to initiate a clinical proof of concept trial of zelpultide alfa in bronchopulmonary dysplasia and in other lung related disorders [15] . An IND for zelpultide alfa in combination with an existing surfactant was expected to be filed with the FDA in the fourth quarter of 2012. The company was in discussion with one of a surfactant manufacturer as of June 2011 [3] .
As of February 2023, preclinical study of zelpultide alfa in influenza and respiratory syncytial virus infections was underway in US (Airway Therapeutics pipeline, February 2023).
In preclinical studies, zelpultide alfa inhibited SARS-CoV-2 replication and promoted viral elimination. The therapeutic also reduced secondary infections in mechanically ventilated COVID-19 patients [13] .
Preclinical data suggested that zelpultide alfa, in addition to commercially available surfactant, effectively prevents the infection, reduces inflammation and lung damage compared to current standard of care [16] . Zelpultide alfa also modulates immune system [17] .
The US FDA and the EMA granted orphan drug designation to zelpultide alfa for the prevention of bronchopulmonary dysplasia [16] .
Financing information
In January 2020, Airway Therapeutics received a oversubscribed series C financing worth $US 15.5 million, the proceeds of which will be used for the clinical development of zelpultide alfa for the prevention of serious respiratory disease bronchopulmonary dysplasia (BPD) in very preterm infants, while also supporting preclinical research in influenza, respiratory syncytial virus (RSV) and cystic fibrosis. The funding will also enable further development its preclinical package for influenza, RSV and cystic fibrosis [17] .
In March 2017, Airway Therapeutics received a funding of $US6.3 million as a part of bridge financing from new and existing investors including Cincinnati Children’s Hospital Medical Center, CincyTech and Queen City Angels. The company plans to utilise the funds for the development of zelpultide alfa which includes, manufacturing, IND enabling studies and clinical proof of concept trials [15] .
In September 2014, Airway Therapeutics secured $US4.6 million in Series A financing. The company will use proceeds for the development of zelpultide alfa, including formulation, manufacturing and designing preclinical studies required in preparation for clinical studies [16] .
Patent Information
Airway Therapeutics has patent protection for zelpultide alfa used for the prevention of bronchopulmonary dysplasia [15] .
Drug Properties & Chemical Synopsis
- Route of administration Intratracheal
- Formulation unspecified
- Class Anti-infectives, Anti-inflammatories, Antivirals, Recombinant proteins
- Target Protein; Virus replication
- Mechanism of Action Cell membrane permeability enhancers; Protein replacements; Virus replication inhibitors
-
WHO ATC code
R07A-A (Lung surfactants)
-
EPhMRA code
R7C (Lung Surfactants)
- CAS Registry Number 2245003-06-7
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Bronchopulmonary dysplasia | - | In neonates, Prevention | Phase I | Spain, USA | Intratracheal / unspecified | Airway Therapeutics | 01 Sep 2021 |
| COVID 2019 infections | - | - | Phase I | USA | Intratracheal / unspecified | Airway Therapeutics | 01 Jan 2021 |
| Inflammation | - | - | Research | USA | unspecified / unspecified | Airway Therapeutics | 27 Feb 2023 |
| Influenza virus infections | - | - | Preclinical | USA | unspecified / unspecified | Airway Therapeutics | 27 Feb 2023 |
| Respiration disorders | - | - | Research | USA | unspecified / unspecified | Airway Therapeutics | 27 Feb 2023 |
| Respiratory syncytial virus infections | - | - | Preclinical | USA | unspecified / unspecified | Airway Therapeutics | 27 Feb 2023 |
Priority Development Status
| Type | Region | Indication |
|---|---|---|
| Coronavirus Treatment Acceleration Program | USA | COVID 2019 infections |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Bronchopulmonary dysplasia | Prevention | European Union | Airway Therapeutics | 10 Sep 2014 |
| Bronchopulmonary dysplasia | Prevention | USA | Airway Therapeutics | 10 Sep 2014 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Airway Therapeutics | Originator | USA |
| Airway Therapeutics | Owner | USA |
| Glycotope | Technology Provider | Germany |
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2023 | Trial Update | Airway Therapeutics plans a phase III trial for Bronchopulmonary dysplasia in North America and Europe by the end of 2023 [9] | 12 Jun 2023 |
| 31 Jan 2021 | Trial Update | Airway Therapeutics plans a phase I in COVID-2019 infections (Intratracheal) in January 2021 (NCT04659122) (700322173) | 07 Jun 2021 |
| 30 Sep 2020 | Regulatory Status | Airway Therapeutics expects to file an Investigational New Drug application (IND) to the US FDA for Bronchopulmonary dysplasia in the third quarter of 2020 [1] | 01 Apr 2021 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 05 Jun 2023 | Trial Update | Airway Therapeutics completes enrolment in its phase Ib trial for Bronchopulmonary dysplasia in USA and Spain [9] Updated 12 Jun 2023 |
| 05 Jun 2023 | Trial Update | Airway Therapeutics plans a phase III trial for Bronchopulmonary dysplasia in North America and Europe by the end of 2023 [9] Updated 12 Jun 2023 |
| 27 Feb 2023 | Phase Change | Early research in Inflammation in USA (unspecified route) (Airway Therapeutics pipeline, February 2023) Updated 31 Mar 2023 |
| 27 Feb 2023 | Phase Change | Early research in Respiration disorders in USA (unspecified route) (Airway Therapeutics pipeline, February 2023) Updated 31 Mar 2023 |
| 27 Feb 2023 | Phase Change - Preclinical | Preclinical trials in Influenza virus infections in USA (unspecified route) (Airway Therapeutics pipeline, February 2023) Updated 31 Mar 2023 |
| 27 Feb 2023 | Phase Change - Preclinical | Preclinical trials in Respiratory syncytial virus infections in USA (unspecified route) (Airway Therapeutics pipeline, February 2023) Updated 31 Mar 2023 |
| 23 Feb 2023 | Trial Update | Airway Therapeutics terminates a phase I trial in COVID-2019 infections in USA (Intratracheal), due to study goals reached (NCT04659122) Updated 19 Jul 2023 |
| 28 Mar 2022 | Trial Update | Airway Therapeutics plans a phase III trial for Bronchopulmonary dysplasia [7] Updated 01 Apr 2022 |
| 01 Sep 2021 | Phase Change - I | Phase-I clinical trials in Bronchopulmonary dysplasia (In neonates, Prevention) in Spain (Intratracheal) (NCT04662151) [5] Updated 09 Oct 2022 |
| 01 Sep 2021 | Phase Change - I | Phase-I clinical trials in Bronchopulmonary dysplasia (Prevention, In neonates) in USA (Intratracheal) (NCT04662151) Updated 01 Apr 2022 |
| 30 Aug 2021 | Regulatory Status | 9333585: Updated KDM with missing trial info and first patient dosing info; Thes sent to add DCs-Anti-inflammatories and Antivirals and map MoA Updated 30 Aug 2021 |
| 12 Apr 2021 | Regulatory Status | Zelpultide alfa receives Coronavirus Treatment Acceleration Program (CTAP) status for COVID-2019 infections in USA [4] Updated 05 Jun 2021 |
| 12 Apr 2021 | Regulatory Status | Airway Therapeutics approves IND application for Zelpultide alfa in COVID-2019 infections [12] Updated 12 Apr 2021 |
| 26 Mar 2021 | Trial Update | Airway Therapeutics plans a pivotal trial for Bronchopulmonary dysplasia (Prevention) [13] Updated 07 Apr 2021 |
| 26 Mar 2021 | Active Status Review | Zelpultide alfa is still in preclinical trial for Bronchopulmonary dysplasia (Prevention) in USA [13] Updated 01 Apr 2021 |
| 26 Mar 2021 | Regulatory Status | Airway therapeutics files IND application for Zelpultide alfa for COVID-2019 infections [13] Updated 01 Apr 2021 |
| 26 Mar 2021 | Regulatory Status | The US FDA approves the IND application for Zelpultide alfa for Bronchopulmonary dysplasia [13] Updated 01 Apr 2021 |
| 26 Mar 2021 | Trial Update | Airway Therapeutics plans a phase Ib trial for Bronchopulmonary dysplasia (Prevention, In neonates) (Intratracheal) (NCT04662151) [13] Updated 01 Apr 2021 |
| 01 Jan 2021 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections in USA (Intratracheal) (NCT04659122) Updated 07 Jun 2021 |
| 14 Dec 2020 | Trial Update | Airway Therapeutics plans a phase I in COVID-2019 infections (Intratracheal) in January 2021 (NCT04659122) Updated 07 Jun 2021 |
| 20 May 2020 | Regulatory Status | Airway Therapeutics expects to file an Investigational New Drug application (IND) to the US FDA for Bronchopulmonary dysplasia in the third quarter of 2020 [1] Updated 01 Apr 2021 |
| 20 May 2020 | Regulatory Status | Airway Therapeutics files an pre-IND application with the US FDA for Bronchopulmonary dysplasia (BPD) before May 2020 [1] Updated 27 May 2020 |
| 12 Mar 2020 | Phase Change | Early research in COVID-2019 infections in USA (unspecified route) [14] Updated 17 Mar 2020 |
| 12 Mar 2020 | Regulatory Status | Airway Therapeutics files regulatory application with the National Institutes of Health (NIH) to evaluate Zelpultide alfa for COVID-2019 infections [14] Updated 17 Mar 2020 |
| 11 Sep 2017 | Licensing Status | Airway Therapeutics in-licenses GlycoExpress cell line technology from Glycotope [2] Updated 19 Sep 2017 |
| 07 Mar 2017 | Active Status Review | Research programme: recombinant human surfactant protein D is still in preclinical development for Bronchopulmonary dysplasia (Prevention) in USA [15] Updated 08 Mar 2017 |
| 07 Mar 2017 | Patent Information | Airway Therapeutics has patent protection for Zelpultide alfa for Bronchopulmonary dysplasia [15] Updated 08 Mar 2017 |
| 07 Mar 2017 | Regulatory Status | Airway Therapeutics announces intention to submit IND to US FDA for Bronchopulmonary dysplasia (Prevention) [15] Updated 08 Mar 2017 |
| 07 Mar 2017 | Trial Update | Airway Therapeutics plans a clinical trial for Bronchopulmonary dysplasia (Prevention) [15] Updated 08 Mar 2017 |
| 16 Jul 2016 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Bronchopulmonary-dysplasia in USA (Intratracheal) Updated 16 Jul 2016 |
| 10 Sep 2014 | Regulatory Status | Zelpultide alfa receives Orphan Drug status for Bronchopulmonary dysplasia (Prevention) in USA Updated 19 Sep 2014 |
| 10 Sep 2014 | Regulatory Status | Zelpultide alfa receives Orphan Drug status for Bronchopulmonary dysplasia (Prevention) in European Union Updated 19 Sep 2014 |
| 03 Jun 2011 | Phase Change - Preclinical | Preclinical trials in Bronchopulmonary dysplasia in USA (Intratracheal) Updated 13 Jun 2011 |
References
-
Airway Therapeutics and Celonic Group Collaborate to Produce AT-100 as Promising New Candidate for Coronavirus.
Media Release -
Airway Therapeutics, LLC Obtains License on Glycotope Cell Line.
Media Release -
New Company Formed to Take Cincinnati Children's Lung Treatment Research to Premature Babies.
Media Release -
Airway Therapeutics gibt die FDA-Zulassung fr zweite Indikation von AT-100 als IND fr COVID-19-Patienten mit schwerem Verlauf bekannt.
Media Release -
Airway Therapeutics Opens International Clinical Trial Sites and Treats First Patient in Spain in Phase 1b Study of Zelpultide Alfa (AT-100) in Preterm Infants at Risk for Bronchopulmonary Dysplasia (BPD).
Media Release -
A Phase 1b, Randomized, Blinded, Dose-Determined Study Evaluating the Safety and Tolerability Profile of Intervention With AT-100 (rhSP-D) in Preterm Neonates at High Risk for the Development of Bronchopulmonary Dysplasia (BPD)
ctiprofile -
Airway Therapeutics Announces First Patient Dosed in Phase 1b Trial of AT-100 in Preterm Infants at Risk for Bronchopulmonary Dysplasia (BPD).
Media Release -
Airway Therapeutics Completes Dose Escalation in Phase 1b Trial of Zelpultide Alfa (AT-100) for Very Preterm Infants at Risk for Bronchopulmonary Dysplasia.
Media Release -
Airway Therapeutics Completes Enrollment in Phase 1b Trial of Zelpultide Alfa (AT-100) for Very Preterm Infants at Risk for Bronchopulmonary Dysplasia.
Media Release -
Airway Therapeutics Announces First Patient Dosed in Phase 1b Trial of AT-100 in Severe COVID-19 Patients.
Media Release -
Phase 1b Open-label, Single Arm, Cohort Dose Escalation Study Evaluating the Safety, Tolerability, and Feasibility of Intervention With AT-100 (rhSP-D) in Intubated Patients Receiving Invasive Mechanical Ventilation With Severe COVID-19 Infection or Respiratory Failure Secondary to Severe Community Acquired Pneumonia
ctiprofile -
Airway Therapeutics Announces FDA Acceptance of IND for AT-100's Second Indication in Severe COVID-19 Patients.
Media Release -
Airway Therapeutics Announces FDA Acceptance of IND for AT-100 in Preterm Infants at Risk for Bronchopulmonary Dysplasia (BPD).
Media Release -
Airway Therapeutics Announces Filing with NIH to Evaluate AT-100 as a Therapy for Novel Coronavirus.
Media Release -
Airway Therapeutics Closes $6.3M in Finance Round.
Media Release -
Airway Therapeutics Raises $4.6 Million in Series A Funding.
Media Release -
Airway Therapeutics Closes $15.5 Million Series C Financing to Advance Preclinical and Clinical Research and Development Programs to Prevent and Treat Serious Respiratory Diseases.
Media Release
Adis International Ltd. Part of Springer Science+Business Media
© Springer Nature Switzerland AG