4D hosts virtual R&D event providing updates on clinical programmes in oncology and COVID-19

Leeds, UK, 5th June, 2020 - 4D pharma plc, a pharmaceutical company leading the development of Live Biotherapeutics, today announces a virtual R&D event in which Duncan Peyton, Chief Executive Officer, 4D pharma, Prof. Axel Glasmacher, Chairman, 4D pharma, and Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma, provide updates on the company’s clinical programmes in oncology and COVID-19. Covering analysts were invited to participated in a Question & Answer session after the presentation.  The presentation slides and a recording are accessible via the “Reports and Presentations” area of 4D’s website at https://www.4dpharmaplc.com.

Clinical update summary: oncology and COVID-19 programmes

Oncology

• Early data supports proof of concept in metastatic renal cell carcinoma, with potential to expand into additional tumour types
• Continuing positive signals further validate the Company’s single strain Live Biotherapeutic approach
• Further clinical confirmation of expected favorable safety profile of therapeutics developed by the Company

COVID-19

• MRx-4DP0004 has a relevant mechanism of action for COVID-19
• Research Ethics Committee and Health Research Authority approval received
• Clinical site selection and initiations underway
• First patient dosing expected June 2020 

Oncology – MRx0518 and Keytruda® Phase I/II Combination Study

The presentation provides additional efficacy results from the ongoing Phase I/II trial of immuno-oncology candidate MRx0518 in combination with Keytruda® in solid tumours. Of the twelve patients who were enrolled in Part A, five are continuing on study treatment.

Two of these five patients had tumours that achieved a partial response (PR). One is a patient with metastatic renal cell carcinoma (mRCC), who has now been on the study for over a year and has received three previous lines of therapy before enrolling on the study.  The other is a patient with metastatic non-small cell lung cancer (mNSCLC) with a mutation in Epidermal Growth Factor Receptor (EGFR). This patient has been on the study for 49 weeks and has had seven previous lines of therapy. NSCLC patients harboring EGFR mutations are reported to be less likely to show clinical benefit from PD-1/PD-L1 checkpoint inhibitors. [1,2,3]

Both of these patients’ tumours showing partial responses to the combination of MRx0518 and Keytruda(R) combined with a PD-1 checkpoint inhibitor had previously shown a response no better than stable disease (SD) to PD-1 checkpoint inhibitor treatment, before developing secondary resistance and progressive disease. 

Three further patients taking part in the study have mRCC and have exhibited stable disease (SD). One has been on the study for 44 weeks, one for 15 weeks and the other for 12 weeks.

Seven of the twelve patients who were enrolled in Part A have been withdrawn from treatment. Two patients were withdrawn due to progressive disease determined at the first scheduled restaging scan at nine weeks.  Three patients were withdrawn following disease-related serious adverse events (SAE) and an early first restaging scan.  Two patients were withdrawn prior to any restaging scan due to SAEs related to disease progression.

Part B of the study is now open to recruitment of an additional 30 patients per tumour type cohort included in the study.  Four additional investigational sites will be opened.

COVID-19 – Phase II Clinical Study

In April, 4D pharma announced receipt of expedited clinical trial authorization (CTA) from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for a Phase II randomized, double-blind, placebo-controlled study in up to 90 patients hospitalized with COVID-19.

The study has now received Research Ethics Committee and Health Research Authority approvals and the Company is in the process of initiating the first clinical sites, with the first subjects expected to be recruited in June. Preliminary data is expected in Q4 2020.

Further summary information on the clinical programmes discussed during the webinar is included below.

1.  Lee CK, Man J, Lord S. et al. Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non-small cell lung carcinoma: a systematic review and meta-analysis. JAMA Oncol 2018; 4(2): 210–216. doi:10.1001/jamaoncol.2017.4427

2.  Lisberg A, Cummings A, Goldman JW. et al. A phase II study of pembrolizumab in EGFR-mutant, PD-L1+, tyrosine kinase inhibitor (TKI) naive patients with advanced NSCLC. J Thorac Oncol 2018; 13(8): 1138–1145. doi: 10.1016/j.jtho.2018.03.035

3.  Borghaei H, Paz-Ares L, Horn L. et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373(17): 1627–1639.  doi: 10.1056/NEJMoa1507643

About 4D

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.

About MRx0518

MRx0518 is single strain Live Biotherapeutic product in development for the treatment of cancer. It is delivered as an oral capsule and stimulates the body’s immune system, directing it to produce cytokines and immune cells that are known to attack tumours. It is currently being evaluated in three clinical trials in cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy study in a variety of solid tumours and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA® (pembrolizumab) in patients who have previously progressed on anti PD-1 therapies. This study is being carried out at MD Anderson (Houston, USA) in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA.  MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer.

About MRx0518-I-002 clinical trial

MRx0518-I-002 (NCT03637803) is a Phase I/II open-label, safety and preliminary efficacy study of MRx0518 in combination with KEYTRUDA(R) (pembrolizumab) in patients with solid tumours (non-small cell lung cancer, renal cell carcinoma, bladder cancer or melanoma) who have previously progressed on anti PD-1/PD-L1 therapy. Subjects are treated with intravenous KEYTRUDA(R) every three weeks and one capsule twice daily of MRx0518. Treatment continues as long as clinically relevant, until disease progression, unacceptable AEs or withdrawal of consent up to a maximum of 35 cycles of KEYTRUDA(R). 

Part A was conducted in 12 patients (of any of the four tumour types) and Part B will be conducted in up to 30 patients of each tumour type.  

This study is being carried out at The University of Texas MD Anderson Cancer Center, Houston, USA, in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA.

For further detail about the study please visit https://clinicaltrials.gov/ct2/show/NCT03637803

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 hospitalized with suspected or confirmed COVID-19. For more information about the clinical study please visit https://clinicaltrials.gov/ct2/show/NCT04363372

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