PulmiCell™ is the most advanced product in our pipeline, with strong late-stage pre-clinical data supporting the move into clinical trials with patients with severe inflammatory and fibrotic components in the disease. Although a specific organ is often targeted, many diseases have a profound systemic inflammatory involvement, and here PulmiCell™ is also ideally suited as a therapeutic. Amniotics™ has recently completed building a GMP grade cell manufacturing facility at our premises in Sweden, allowing us to produce PulmiCell™ for an Investigational New Drug (IND) program including pre-clinical studies and clinical trials. On the successful completion of this program, we expect a high interest from other commercial entities in the Pharma-sector for further rapid development of PulmiCell™ clinical programs.
About different diseases that can be treated with PulmiCell
The worldwide outbreak of the novel Coronavirus, SARS-CoV-2, which can lead to a previously unidentified viral pneumonia, which has now been named COVID-19 has the world scrambling for a cure. Several anti-virals (e.g. Remdesivir) and disease modulating drugs (Plaquenil) are being investigated, and many of these are used ”off-label” in the treatment of severe cases. Despite all the efforts, mortality of COVID-19 remains high. Moreover, the treatment duration in the intensive care unit (ICU) is long, up to several weeks, thereby blocking each bed and ventilator from treating a new patient. Thus, new therapeutic options are in dire need. Promising data has been published by a group based in Singapore using mesenchymal stem cells on a small group (n=7) of COVID-19 patients where the MSC’s treatment arm clearly fared better. The published data, indicates that the MSC’ downregulate the so-called cytokine storm, thereby helping the patients to recover.
We have strong pre-clinical data to support that PulmiCell™ will have relevant and significant effects modulating the systemic inflammatory response in COVID-19. Moreover, PulmiCell™ contains lung specific MSCs expected to selectively home to the damaged lung and aiding the healing process. Importantly, PulmiCell™ does not express the entry protein (ACE2) for the coronavirus SARS-CoV-2, hereby being able to avoid being infected and destroyed by the virus. There are several trials ongoing in China with MSCs for Severe COVID-19 (e.g. NCT04288102 & NCT04293692), and correspondingly US Biomedical Advanced Research and Development Authority (BARDA) has designated a product based on MSC-like cells as highly relevant for this disease.
We are therefore preparing a clinical trial for the use of PulmiCell™ in COVID-19 patients. The start date is aimed for summer 2020.
PulmiCell™ is administered as a single dose intravenous injection. The injected stem cells home to damaged sites and aid healing, as well as reducing systemic inflammation.
Figure 1 apoptotic cell (blue) heavily infected with SARS-COV-2 virus particles (yellow)
Courtesy: National Institute of Allergy and Infectious Diseases (NIAID).
Idiopathic Pulmonary Fibrosis (IPF)
Another candidate for MSC-based treatment is Idiopathic Pulmonary Fibrosis (IPF), a type of interstitial lung disease characterized by progressive fibrosis and scarring within the lungs, altering their normal function. This build-up of scar tissue progressively prevents the lungs from effectively transporting oxygen into the bloodstream. Common symptoms of IPF are shortness of breath (dyspnea) and a persistent dry, hacking cough, while some patients also develop lung cancer, pulmonary emboli, pneumonia, or pulmonary hypertension.
The incidence and prevalence of IPF is rising worldwide. In Europe there is for instance evidence of a doubling in patient numbers over a ten-year period in both the UK and Czech Republic. Furthermore, mortality in IPF is high, with a reported median survival of 2–3 years from diagnosis, and only around 20% survival at 5 years. Interestingly, there is a significant disparity between genders, with mortality rates in the range of 0.41–12.1 per 100,000 for European men and 0.24–5.63 per 100,000 for women. Despite its rare disease status, IPF represents a significant burden to society. In 2011, the mean annual health care cost for an IPF patient in Denmark was €21,184, seven times higher than the year before diagnosis, and employment income for these patients was halved compared to age-matched controls.
Treatment options for IPF are limited, with only two therapies approved for IPF in the world today. These are the antifibrotic drugs, Ofev (Nintedanib, Boehringer Ingelheim) and Esbriet (Pirfenidone, Genentech), both disease-modifying agents which slow disease progression but are unable to reverse disease progress in patients. Moreover, both therapies lead to major gastrointestinal (e.g. nausea, vomiting and diarrhea) and hepatic (incl. liver damage) adverse effects, and Esbriet is linked to skin-related adverse effects such as rash and photosensitivity, limiting the patient population able to be treated with these drugs.
Our solution, PulmiCell™, is an Advanced Therapy Medicinal Product (ATMP) consisting of MSCs derived from Term Amniotic Fluid (TAF). PulmiCell™, is designed to be used as an MSC-based therapy for IPF. The cells will be administered by a single i.v. injection, after which they migrate into the damaged lung where they secrete bioactive molecules, reduce inflammation, promote tissue regeneration, and slow fibrosis.