Coronavirus fibroblast cell therapy - FibroGenesis
Alternative Names: Pneumoblast™Latest Information Update: 20 Oct 2020
At a glance
- Originator FibroGenesis
- Class Fibroblast cell therapies; Gene therapies
- Mechanism of Action Cell replacements
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Preclinical SARS-CoV-2 acute respiratory disease
Most Recent Events
- 06 Oct 2020 Fibrogenesis plans clinical trial for SARS-COV-2 acute respiratory disease in Brazil
- 06 Oct 2020 Fibrogenesis plans clinical trial for SARS-COV-2 acute respiratory disease in USA
- 01 Oct 2020 Fibrogenesis collaborates with R4D Biotech for clinical trial in SARS-COV-2 acute respiratory disease in Brazil
Development Overview
Introduction
Human dermal fibroblast (HDFs) based cell therapy, designated as PneumoBlast, is being developed by FibroGenesis for the treatment of SARS-COV-2 acute respiratory disease. The therapy comprises of proprietary universal donor fibroblasts. The therapy addresses acute respiratory distress syndrome by making use of fibroblasts as toll-like receptors which activates fibroblasts as a means to suppress acute respiratory distress syndrome (ARDS), while producing factors such as inteferons to stimulate anti-viral immunity.. In preclinical studies the therapy has shown to reduce pulmonary pathology associated with ARDS as well as protects or regenerates type II pulmonary epithelial cells. Preclinical development is underway in the US.
Company Agreements
In October 2020, FibroGenesis entered into a clinical collaboration agreement with R4D Biotech to conduct clinical trial of coronavirus fibroblast cell therapy for the treatment of acute respiratory distress syndrome (ARDS) in patients with COVID-2019 infections in Brazil. Both companies will collaborate on a clinical study design that will meet the needs of patients in Brazil. Financial details were not disclosed.
[1]
Key Development Milestones
In August 2020, FibroGenesis reported results from the preclinical studies which showed that admixing of fibroblast cell therapy with activated monocyte or endothelial cells resulted in significant inhibition of tissue factor expression [2] .
As of July 2020, FibroGenesis is seeking to conduct experiments in animal models of SARS-Cov-2 and toxicity evaluation to support the US FDA Investigational New Drug (IND) filing to enable clinical trials (FibroGenesis website, July 2020) [3] .
In July 2020, FibroGenesis reported that the results from the preclinical data demonstrated that administration of the fibroblast cell therapy resulted in alterations of cytokines known to be associated with survival and recuperation from COVID-19 infections [4] . Updated results from animal model in preclinical studies were released by the FibroGenesis in July 2020 [3] .
In May 2020, FibroGenesis reported that in an animal model of lung inflammation which resembles COVID-19, the fibroblast cell therapy caused significant reduction in lung fluid accumulation [5] .
Patent Information
In April 2020, FibroGenesis filed a US patent No.63/002,134 entitled, "Peptides and Adjuvants for Augmentation of Fibroblast Therapy for Coronavirus." The patent claims include utilisation of fibroblast cells along with adjuvants like peptides and hydroxychloroquine which stimulates the production of natural interferon to suppress the viral infection and corresponding "cytokine storm." [6] .
In March 2020, FibroGenesis filed a US patent No.62 986 339 entitled, "Fibroblast and TLR Activated Fibroblast Treatment of Viral Induced Acute Respiratory Distress Syndrome." The patent claims include utilisation of universal donor cell therapies for treatment of acute respiratory distress syndrome (ARDS) [7] .
Drug Properties & Chemical Synopsis
- Route of administration Parenteral
- Formulation unspecified
- Class Fibroblast cell therapies, Gene therapies
- Target Cell
- Mechanism of Action Cell replacements
-
WHO ATC code
V03A-X (Other therapeutic products)
-
EPhMRA code
V3X (All Other Therapeutic Products)
Table of Contents
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| SARS-CoV-2 acute respiratory disease | - | - | Preclinical | USA | Parenteral / unspecified | FibroGenesis | 01 Apr 2020 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| FibroGenesis | Originator | USA |
| FibroGenesis | Owner | USA |
Scientific Summary
Pharmacodynamics
Summary
Updated results from bleomycin model of lung scarring demonstrated that administration of fibroblast cell therapy showed 51% reduction in lung fibrosis (p < 0.005). Fibroblast therapy demonstrated 221% more effectiveness as compared to bone marrow derived mesenchymal stem cells. Fibroblast therapy also showed 192% more effectiveness in producing the potent anti-inflammatory protein interleukin 1 receptor antagonist as compared to bone marrow derived mesenchymal stem cells (p < 0.005) [3] . Results from preclinical studies showed that administration of fibroblast cell therapy resulted in reduced concentrations of the inflammatory cytokines interleukin-1 beta, interleukin-6, interleukin-8, interleukin-17, interleukin-18, and Tumor Necrosis Factor alpha, TNFa. The therapy also caused an increase in anti-inflammatory cytokines interleukin-4, interleukin-10, interleukin-13 and interleukin-35, as well as regeneration-associated cytokines FGF-2 and HGF-1. Earlier results from an animal mouse model of lung inflammation showed that mice treated with lipopolysaccharide caused an increase of the lung wet weight to body weight (LWW/BW) ratio of 12.5 mg/g. Administration of bone marrow mesenchymal stem cells (BMSCs) to lipopolysaccharide-treated-mice only reduced the LWW/BW ratio to 9.9 mg/g. Fibroblast administration significantly reduced the LWW/BW ratio to 5.2 mg/g in lipopolysaccharide-treated-mice (p < 0.001). The therapy showed a 37% improvement in outcome compared to BMSCs, which was statistically significant (p < 0.005). The average LWW/BW ratios returned to baseline control numbers of healthy lungs, which resulted in no statistical difference between recovered lungs and normal/healthy lungs using the cell therapy. Assessment of lung inflammation marker interleukin-6 showed that control mice possessed 532.3 pg/ml of the cytokine, whereas lipopolysaccharide administration caused an increase to 4400.1 pg/ml. Treatment with BMSCs resulted in a slight 26% decrease of IL-6 in the lipopolysaccharide-treated-mice to 3317.7 pg/ml, whereas the cell therapy significantly reduced IL-6 by 80% to 896.2 pg/ml, (p < 0.001). The use of fibroblast cell therapy resulted in a 54% improvement compared to BMSCs (p <0.001). A reduction of inflammation in 24 hours back to normal/healthy lung levels was observed with the cell therapy [4] [5] .
In preclinical studies, admixing of fibroblast cell therapy with activated monocyte or endothelial cells demonstrated significant inhibition of tissue factor expression. Treatment of activated monocytes with fibroblast cell therapy resulted in a 77% reduction of tissue factor expression as compared to untreated monocytes (p< 0.001). Mixture of mesenchymal stem cells with activated monocytes resulted in a 13% inhibition of tissue factor expression (p= 0.01). Moreover, in activated endothelial cells, fibroblast therapy decreased expression of tissue factor by 80% (p< 0.001), whereas mesenchymal stem cells resulted in a 30% (p= 0.01) reduction [2] .
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 06 Oct 2020 | Trial Update | Fibrogenesis plans clinical trial for SARS-COV-2 acute respiratory disease in Brazil [1] Updated 20 Oct 2020 |
| 06 Oct 2020 | Trial Update | Fibrogenesis plans clinical trial for SARS-COV-2 acute respiratory disease in USA [1] Updated 20 Oct 2020 |
| 01 Oct 2020 | Licensing Status | Fibrogenesis collaborates with R4D Biotech for clinical trial in SARS-COV-2 acute respiratory disease in Brazil [1] Updated 20 Oct 2020 |
| 12 Aug 2020 | Scientific Update | Pharmacodynamics data from a preclinical trial in SARS-COV-2 acute respiratory disease released by FibroGenesis [2] Updated 18 Aug 2020 |
| 21 Jul 2020 | Scientific Update | Pharmacodynamics data from a preclinical trial in SARS-COV-2 acute respiratory disease released by FibroGenesis [3] Updated 17 Aug 2020 |
| 09 Jul 2020 | Regulatory Status | FibroGenesis announces intention to submit IND to the US FDA for SARS-COV-2 acute respiratory disease, before July 2020 (FibroGenesis website, July 2020) Updated 17 Aug 2020 |
| 09 Jul 2020 | Trial Update | FibroGenesis plans a clinical trial for SARS-COV-2 acute respiratory disease in USA, before July 2020 (FibroGenesis website, July 2020) Updated 17 Aug 2020 |
| 01 Jul 2020 | Scientific Update | Pharmacodynamics data from a preclinical trial in SARS-COV-2 acute respiratory disease released by FibroGenesis [4] Updated 17 Aug 2020 |
| 21 May 2020 | Scientific Update | Pharmacodynamics data from a preclinical trial in SARS-COV-2 acute respiratory disease released by FibroGenesis [5] Updated 17 Aug 2020 |
| 01 Apr 2020 | Patent Information | FibroGenesis files for patent protection with the USPTO for utilisation of fibroblast cells along with adjuvants for coronavirus [6] Updated 06 Apr 2020 |
| 01 Apr 2020 | Phase Change - Preclinical | Preclinical trials in SARS-COV-2 acute respiratory disease in USA (Parenteral) [6] Updated 06 Apr 2020 |
| 10 Mar 2020 | Patent Information | FibroGenesis files for patent protection with the USPTO for Coronavirus fibroblast cell therapy [7] Updated 13 Mar 2020 |
| 10 Mar 2020 | Phase Change | Early research in SARS-COV-2 acute respiratory disease in USA (Parenteral) [7] Updated 13 Mar 2020 |
References
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FibroGenesis Expands Fight Against COVID-19 In Brazil with International Collaboration.
Media Release -
FibroGenesis Reports Breakthrough in Prevention of COVID-19 Blood Clotting.
Media Release -
COVID-19 Fibroblast Based Cell Therapy Candidate Shown to Reduce Lung Scarring in Aggressive Animal Model.
Media Release -
FibroGenesis Identifies Mechanism Responsible for Blocking COVID19-Like Lung Inflammation.
Media Release -
FibroGenesis Reports COVID-19 Breakthrough Using Fibroblast Cell Therapy (Pre-Clinical Trial Phase).
Media Release -
FibroGenesis Files Expanded Patent Coverage for its Fibroblast Cell Therapy to treat Coronavirus (COVID-19) ARDS.
Media Release -
FibroGenesis Files Patent Using its Fibroblast Cell Therapy for Coronavirus (COVID-19) ARDS.
Media Release
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