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4D pharma announces publication of preclinical research showing single strain Megasphaera Massiliensis improves activity of CAR-T

Leeds, UK, July 6, 2021 – 4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, today announces the publication of pre-clinical research relating to its second-generation immuno-oncology LBP MRx1299 improving the activity of CAR-T.

The research, conducted in collaboration with the Philipps-University Marburg, Germany, and Universitätsklinikum Würzburg, Germany, and published in Nature Communications, demonstrates the ability of the bacterium Megasphaera massiliensis or its short chain fatty acid (SCFA) metabolite pentanoate to enhance the anti-tumor activity of cytotoxic T lymphocytes (CTL) and CAR-T therapies in animal models of cancer, resulting in better tumor clearance.

4D pharma identified M. massiliensis MRx1299 using its MicroRx(R) platform and previously showed MRx1299 to have specific histone deacetylase (HDAC) inhibitory activity and be a rare prolific producer of pentanoate.  This led to discussions with the lab of Dr. Alexander Visekruna, corresponding author on the recent publication, due to their work investigating the effects of SCFAs on immune cell subsets.

“Our existing clinical oncology programs, such as the study of MRx0518 and Keytruda in refractory patients, have shown the important role our live biotherapeutics have to play in the fight against cancer in combination with immunotherapies. Using the MicroRx platform we have now shown we have the potential to improve the efficacies of cell therapies such as CAR-T,” commented Dr. Imke Mulder, Research Director, 4D pharma. “This demonstrates not only the importance of Live Biotherapeutics as a new modality poised to revolutionize the treatment of a wide range of cancers, but also the power of our MicroRx platform to continue making significant discoveries and advances in this field.”

“Collectively, these results suggest that low-abundant commensal bacterial species such as M. massiliensis and their selective metabolites such as pentanoate, rather than broadly distributed and abundant commensals, may be used as specific microbial biotherapeutics to enhance anti-tumor immunity and increase the efficacy of CAR-T therapy for treating tumors,” commented Dr Alexander Visekruna of the Institute for Medical Microbiology and Hospital Hygiene at Philipps-University Marburg. “Combined therapies including immune checkpoint inhibitors or CAR-T and simultaneous provision of low-abundant bacteria synthesizing specific metabolites as an adjunctive agent may be therapeutically useful.”

Luu et al., Nature Communications, ‘Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer’

About 4D pharma
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(R), that rationally identifies Live Biotherapeutics based on a deep understanding of function and mechanism.

4D pharma's Live Biotherapeutic products (LBPs) are orally delivered single strains of bacteria that are naturally found in the healthy human gut. The Company has five clinical programs, namely a Phase I/II study of MRx0518 in combination with KEYTRUDA (pembrolizumab) in solid tumors, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumors, a Phase I study of MRx0518 in patients with pancreatic cancer, a Phase I/II study of MRx-4DP0004 in asthma, and Blautix(R) in Irritable Bowel Syndrome (IBS) which has completed a successful Phase II trial. 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.

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Last Updated: 06-Jul-2021