On July 25, 2019 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, reported an update on its oncology programmes (Press release, 4d Pharma, JUL 25, 2019, View Source [SID1234537775]). 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.
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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
0MRx0518, 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 View Source