DDDD.L Regulatory News (DDDD)

Non-Regulatory

 4D pharma plc

(the "Company" or "4D")

Oncology Programmes Update

4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, today announces an update on its oncology programmes. New preclinical data on the Company's oncology candidates, MRx0518 and MRx1299, were presented at 1st Microbiome Movement Oncology Response Summit in Boston, USA by Research Director Imke Mulder. A clinical progress update on MRx0518 was also provided by 4D's Chief Scientific Officer, Alex Stevenson.

MRx1299

MRx1299 is a second-generation Live Biotherapeutic identified by 4D's MicroRx® discovery platform. One of the target host pathways identified for this Live Biotherapeutic is its potent histone deacetylase (HDAC) inhibition mediated by bacterial short-chain fatty acids (SCFAs). HDAC inhibition is thought to have multiple modes of anti-cancer activity, acting on both tumour and immune cells. Treatment with MRx1299 and its metabolites gives cytotoxic T lymphocytes the ability to reduce tumour growth in preclinical cancer models.

MRx0518

MRx0518, the Company's lead Live Biotherapeutic candidate in oncology, induces strong innate and adaptive immune responses in vitro and in vivo.  New data presented demonstrates the ability of orally administered MRx0518 to modulate the frequency of immune cell populations with anti-tumour activity in the gastrointestinal tract, systemically and in the tumour microenvironment, acting through signalling pathways known to drive anti-cancer immunity. 

The Company has previously published data on the mechanism of action of MRx0518 (Lauté-Caly et al. 2019), demonstrating that the bacterial flagellin protein, FliC, strongly activates immunostimulatory NF-κB signalling, via the TLR5 receptor. Research presented at the conference indicates a role for additional host receptors, including TLR9, in mediating the immuno-stimulatory effects of MRx0518.

Alex Stevenson, 4D's Chief Scientific Officer, commented: "The identification of our new Live Biotherapeutic candidate, MRx1299, strengthens our leading oncology portfolio and expands the scope of oncology indications for our Live Biotherapeutics. MRx1299 has a different mechanism of action to MRx0518 and as such may be suitable for the treatment of different types of cancer. Studies of MRx1299's efficacy in preclinical models of additional tumour types are ongoing, as is scale-up and process development."

He added, "The additional preclinical data on MRx0518 strengthens our knowledge of its mechanism of action and capacity to launch an immune response against cancer cells. In parallel, data generated from our ongoing clinical studies will assess the ability of MRx0518 to induce these anti-tumour immunological effects in patients. Our Phase I/II study of MRx0518 in combination with KEYTRUDA® (pembrolizumab) in patients with solid tumours will provide us with specific biomarker data from both parts of the study. We anticipate the first of this data to be available by the end of 2019."

A copy of the presentations given can be found at https://www.4dpharmaplc.com/en/newsroom/posters-and-publications

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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 four 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® (pembrolizumab) in solid tumours, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumours and a Phase I/II study of MRx-4DP0004 in asthma. Other focus programmes include disease areas such as 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 unique response mediated by TLR5.

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® (pembrolizumab) in patients with solid tumours who have failed prior anti-PD-1 therapy. A Phase Ib randomised, placebo-controlled study of MRx0518 as a monotherapy in a neoadjuvant setting for solid tumours has also commenced.

For more information about the clinical studies please visit https://clinicaltrials.gov/ct2/show/NCT03851250 

https://clinicaltrials.gov/ct2/show/NCT03934827

About MRx1299

MRx1299 is a second generation Live Biotherapeutic identified through 4D's MicroRx® platform. MRx1299 has strong histone deacetylase (HDAC) inhibition activity. The HDAC pathways are implicated in the development and growth of a range of solid and haematologic cancers. MRx1299 has demonstrated the ability to inhibit tumour growth in models of melanoma and CRC.

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

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