Second-generation Live Biotherapeutic Identified and
Mechanistic Data on MRx0518 and MRx1299 Presented
LEEDS, England, July 25, 2019 /PRNewswire/ -- 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
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
https://www.4dpharmaplc.com/en/newsroom/posters-and-publications
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
For further information please contact:
4D
|
|
Duncan Peyton, Chief
Executive Officer
|
+ 44 (0) 113 895
0130
|
Fay Weston, Head of
Investor Relations
|
+ 44 (0) 799 038
1713
|
|
|
N+1 Singer -
Nominated Adviser and Joint Broker
|
+ 44 (0) 207 496
3000
|
Aubrey Powell/ Justin
McKeegan/ Alex Bond (Corporate Finance)
|
|
Tom Salvesen
(Corporate Broking)
|
|
|
|
Bryan Garnier
& Co. Limited - Joint Broker
|
+ 44 (0) 207 332
2500
|
Dominic Wilson /Phil
Walker
|
|