4D pharma announces expedited UK regulatory acceptance to commence Phase II study in COVID-19

Leeds, UK, April 20, 2020 - 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, today announces that it has received expedited acceptance from the UK Medicines and Healthcare products Regulatory Agency (MHRA) to commence a Phase II study of MRx-4DP0004 in patients with COVID-19.

“As the global SARS-CoV-2 pandemic has developed and the UK has emerged as one of the worst affected areas, 4D pharma has worked intensively with our clinical collaborators and regulatory agencies to bring an urgently needed potential therapy to patients as rapidly as possible” said  Alex Stevenson, Chief Scientific Officer, 4D pharma. “If, as we believe, MRx-4DP0004 is successful in this study it would represent a highly significant breakthrough in the fight against the coronavirus pandemic.”

Current evidence suggests a reason for the high mortality rate of COVID-19 may be due to the hyper-inflammatory response and cytokine storm syndrome caused by uncontrolled activation of the immune system. There is an urgent need for a safe and effective therapy to prevent and treat the severe inflammatory symptoms of COVID-19, to alleviate the significant burden on hospitals and intensive care units (ICUs).  Targeted immunomodulation may be beneficial in these patients.  

4D pharma’s Live Biotherapeutic MRx-4DP0004 is the first immunomodulatory therapy being tested in patients hospitalised with COVID-19 which has shown the potential to simultaneously down-regulate specific pathological aspects of the hyper-inflammatory response while maintaining the appropriate anti-viral response. As MRx-4DP0004 is not broadly immunosuppressive, it does not carry the inherent side-effects associated with immunosuppressants currently under investigation, such as increased risk of infections or cancer, that may preclude their use earlier in more mild-to-moderate patients, which is crucial to reducing the burden on health systems. 

MRx-4DP0004 is an orally administered, single-strain Live Biotherapeutic product (LBP) currently in a Phase I/II clinical trial for the treatment of patients with partly-controlled asthma. 4D pharma has previously shown that MRx-4DP0004 is able to significantly reduce lung inflammation and impact particular immune cell types and pathways implicated in the hyperinflammatory response to SARS-CoV-2 infection. 

MRx-4DP0004 has a highly attractive safety profile with no drug-related adverse safety signals observed in preclinical studies or in patients dosed to date. As such, 4D pharma believes MRx-4DP0004 may be safely administered to patients hospitalised with COVID-19 symptoms to prevent or reduce the onset of severe inflammation.

The COVID-19 Phase II study of MRx-4DP0004 will be a randomised, double-blind, placebo-controlled trial. It will evaluate the efficacy and safety of MRx-4DP0004 in addition to standard-of-care in up to 90 patients hospitalised with symptoms indicative of COVID-19. Eligible participants will be randomised 2:1 to receive 14 days of treatment with either MRx-4DP0004 or placebo (two capsules twice daily). Participants will be monitored daily throughout the treatment period for improvement or progression of COVID-19 symptoms and adverse events. Following completion of the treatment period, participants will be followed-up at approximately 14 and 28 days post treatment. 

The primary endpoint of the trial will be the mean change in clinical status score as measured by the WHO Ordinal Scale for Clinical Improvement. Secondary endpoints include safety and tolerability as well as a suite of additional measures of clinical efficacy including the need for and duration of ventilation.

The study’s Lead Investigator, Dr. Dinesh Saralaya, Consultant Respiratory Physician and Associate Director of Research at Bradford Teaching Hospitals NHS Foundation Trust, and the National Institute for Health Research’s (NIHR) Clinical Lead for Respiratory industry studies, commented, “The COVID-19 pandemic presents an unprecedented challenge to our healthcare systems and we desperately require the rapid development of new therapies to ease the burden on our intensive care units. Given the scale and urgency of the situation it is vitally important that we generate evidence to support the use of new candidates as quickly as possible, before these can be rolled out to patients who need them. As well as its appropriate mechanism of action, the highly favourable safety profile of MRx-4DP0004 makes it a particularly attractive candidate for COVID-19 patients, and may potentially allow us to prevent or delay their progression to requiring ventilation and intensive care.”

About 4D pharma

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 five 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 and a Phase I/II study of MRx-4DP0004 in asthma. Preclinical-stage programmes 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.

For more information, refer to https://www.4dpharmaplc.com.

About MRx-4DP0004 

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 and EU, 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.