DDDD.L Regulatory News (DDDD)

4D pharma plc

(the "Company" or "4D")

Clinical Update - MRx0518 oncology programmes

4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, today announces an update on the clinical progress of its lead oncology Live Biotherapeutic, MRx0518.

Update on MRx0518 Phase I/II combination study with KEYTRUDA® (pembrolizumab)

The first patient participating in the combination phase I/II study of MRx0518 and *KEYTRUDA® in collaboration with Merck & Co., Inc., Kenilworth, NJ., USA and 4D's strategic collaboration with MD Anderson has completed Cycle 1 of Part A of the study with no dose limiting toxicities. This study is open-label and will recruit up to 132 patients with metastatic cancer across multiple cancer types (non-small cell lung cancer, renal cell carcinoma, bladder cancer and melanoma) who have failed prior anti-PD-1 therapy. Part A of the study will enrol 12 patients with the primary outcome measure to assess safety and tolerability. Patients will continue on therapy with follow-up assessments including the anti-tumour effect of the combination. Recruitment is progressing as expected and we anticipate completing Part A before the end of 2019. At this point, Part B of the study, which has a primary endpoint to assess the clinical benefit of the combination, will commence.

Commencement of Phase I MRx0518 neoadjuvant monotherapy

In addition, our phase I study of MRx0518 in a neoadjuvant setting has commenced. This placebo-controlled, phase I study at Imperial College London will evaluate MRx0518 as a monotherapy neoadjuvant in up to 120 treatment-naïve patients with solid tumours (melanoma, prostate, breast, ovarian, urothelial/bladder, renal, lung and head and neck cancers) who are due to undergo surgery as their first treatment. The primary endpoints of this study are safety and tolerability with secondary endpoints including tumour biomarker response, survival, immunological biomarkers and microbiome profiles. The principal investigator for this study is Dr. Jonathan Krell.

This study builds on the recently published data on the mechanism of action of MRx0518 that identified the bacterial flagellin (a specific component of the bacterium) as a potent stimulant of the innate and adaptive immune systems that interacts with the host TLR5 pathway known to be associated with the body's response to cancer. Oncology is a core area of development at 4D and the focus on expanding clinical programmes in this space demonstrates 4D's commitment to this disease area.

Duncan Peyton, 4D's Chief Executive Officer, commented: "We are delighted with the clinical progress of our oncology programme. The first patient completing Cycle 1 with no dose limiting toxicities gives us confidence that we may be able to report on early results of this study this year. The commencement of the monotherapy study will significantly strengthen our understanding of the potential of MRx0518 to impact treatment across a range of cancer settings. The novel study design will, for the first time, enable the evaluation of the anti-tumour immunological effects of a Live Biotherapeutic in treatment-naïve patients who will not be receiving concurrent therapy. We see our continued research and focus on the mechanism of action of our Live Biotherapeutic products as crucial to their further clinical development and regulatory approval as we build our oncology franchise."

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About 4D

Founded in February 2014, 4D 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 that rationally identifies novel bacteria 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. 4D has three clinical studies in progress, namely a phase II clinical study of Blautix in Irritable Bowel Syndrome, a phase I/II study of MRx0518 in combination with Keytruda® in solid tumours and a phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumours. Other focus programmes include disease areas such as asthma and CNS disease. 

About Cancer

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Globally, it is estimated that there were around 18 million new cases in 2018 and that almost 10 million people died of cancer, making it the leading cause of death world-wide. The number of new cancer cases per year is expected to rise to 23.6 million by 2030. The global market for oncology drugs is expected to reach $111.9bn by 2020.

The microbiome has been implicated in cancer treatment and response in a range of clinical settings including standard chemotherapy. The microbiome profile of patients has been demonstrated to drive response to anti-PD-1 therapy in both melanoma and non-small cell lung cancer.

About MRx0518

As both a monotherapy and in combination settings MRx0518 has demonstrated robust efficacy as an immuno-stimulant and anti-tumour agent in multiple tumour models such as breast cancer, renal cell carcinoma and lung cancer. MRx0518 acts on both the innate and adaptive immune system to induce a response mediated by TLR-5.

The Company is investigating MRx0518 across a range of clinical cancer settings in 2019. In collaboration with Merck, Sharpe & Dohme (Merck & Co. Inc), MRx0518 is being evaluated in an open label Phase I/II study of MRx0518 in combination with Keytruda® in patients with solid tumours who have failed prior anti-PD-1 therapy. A phase I randomised, placebo-controlled study of MRx0518 as a monotherapy in a neoadjuvant setting for solid tumours has also commenced.

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

*KEYRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA