Dosing of first patients expected to commence shortly
Leeds, UK, 2 July, 2020 – 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, today announces that its Phase II clinical trial of oral immunomodulator MRx-4DP0004 for patients hospitalised with COVID-19 is now open to enrolment, and dosing of the first patients is expected shortly.
The Phase II randomized, double-blind, placebo-controlled trial is enrolling up to 90 patients admitted to hospital with COVID-19 in the UK. Eligible patients will receive daily oral MRx-4DP0004 or placebo, in addition to standard supportive care. The primary endpoint of the trial is the mean change in clinical status score as measured by the WHO Ordinal Scale for Clinical Improvement. In addition, a number of secondary endpoints assess measures of clinical efficacy including the need for, and duration of, ventilation, in addition to safety and tolerability.
4D pharma’s Live Biotherapeutic MRx-4DP0004 has shown the potential to simultaneously down-regulate specific pathological aspects of the hyper-inflammatory response to viral infection, while maintaining the appropriate anti-viral response. Both are key factors in the effective treatment of the respiratory symptoms associated with COVID-19, not only for hospitalised patients with more severe disease but potentially also in patients with milder symptoms to prevent disease progression and hospitalisation.
As a Live Biotherapeutic, MRx-4DP0004 is expected to display a favourable safety profile. In an ongoing asthma study MRx-4DP0004 has demonstrated an excellent safety profile to date. Particularly in the context of the COVID-19 crisis, the safety of this Live Biotherapeutic is critical, in contrast to the known side-effect profiles of other therapies in clinical trials for COVID-19.
Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma commented, “Reducing hyperinflammation, particularly in the lungs, is key to preventing the exacerbation of symptoms associated with more severe COVID-19. 4D pharma has shown MRx-4DP0004 has the ability to target inflammation in the lungs, potentially reducing the respiratory issues central to COVID-19. 4D pharma aims to use this study to generate robust, meaningful clinical data that will support a safe immunomodulatory Live Biotherapeutic intervention for patients hospitalised with COVID-19.”
He added, “Immunomodulatory intervention in COVID-19 is supported by recent positive results from the UK’s RECOVERY trial, showing dexamethasone reduces the risk of death in hospitalised patients. We believe MRx-4DP0004 has a mechanism of action that may be complementary to that of dexamethasone, which has now become standard-of-care across the UK’s National Health Service (NHS). Importantly, in our ongoing asthma study the addition of MRx-4DP0004 to glucocorticoid treatments (the same class of medicines as dexamethasone) has to date been safe and well tolerated, positioning MRx-4DP0004 to be able to progress rapidly in this new standard-of-care setting. 4D pharma intends to develop MRx-4DP0004 to prevent hospitalised COVID-19 patients deteriorating to the point of needing invasive ventilation and intensive care, and thus alleviate the greatest burdens facing healthcare services. Following positive data from the COVID-19 clinical trial, 4D pharma intends to explore the potential utility of MRx-4DP0004 in additional viral infections like influenza.”
MRx-4DP0004 is a single-strain Live Biotherapeutic in development for the treatment of asthma and COVID-19. It has demonstrated strong and significant efficacy in industry standard preclinical models of steroid-resistant severe asthma. MRx-4DP0004 was shown to reduce both neutrophils and eosinophils in prophylactic and therapeutic settings in vivo. The efficacy was also reflected in a reduction in histopathological lung inflammation, and specific subsets of T cells, dendritic cells and inflammatory cytokines.
4D is currently investigating MRx-4DP0004 in a Phase I/II study in patients with partly-controlled asthma. The study, taking place at sites across the UK, is evaluating the safety and preliminary clinical efficacy of MRx-4DP0004 in addition to standard maintenance therapy such as inhaled corticosteroids (ICS) and long acting beta agonists (LABA), in up to 90 patients. For more information about the clinical study please visit https://clinicaltrials.gov/ct2/show/NCT03851250 .
The Company has received expedited acceptance from the MHRA to conduct a Phase II study of MRx-4DP0004 in up to 90 patients hospitalised with suspected or confirmed COVID-19. For more information about the clinical study please visit https://clinicaltrials.gov/ct2/show/NCT04363372 .
Founded in February 2014, 4D pharma is a world leader in the development of Live Biotherapeutics, a novel and emerging class of drugs, defined by the FDA as biological products that contain a live organism, such as a bacterium, that is applicable to the prevention, treatment or cure of a disease. 4D has developed a proprietary platform, MicroRx®, that rationally identifies Live Biotherapeutics based on a deep understanding of function and mechanism.
4D’s Live Biotherapeutic Products are orally delivered single strains of bacteria that are naturally found in the healthy human gut. The Company has six clinical studies in progress, namely a Phase II clinical study of BLAUTIX® in Irritable Bowel Syndrome (IBS), a Phase I/II study of MRx0518 in combination with KEYTRUDA® (pembrolizumab) in solid tumours, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumours, a Phase I study of MRx0518 in patients with pancreatic cancer, a Phase I/II study of MRx-4DP0004 in asthma, and a Phase II study of MRx-4DP0004 in patients hospitalised with COVID-19. Preclinical-stage programs include candidates for CNS disease such as Parkinson’s disease and other neurodegenerative conditions. The Company has a research collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, to discover and develop Live Biotherapeutics for vaccines.