- One presentation details baseline
biomarkers associated with clinical benefit from MRx0518,
indicating a potential tumor biomarker predictive of response
- The second presentation describes gene and
metagene signature changes with MRx0518 monotherapy demonstrating
anti-tumor immune activation
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 new biomarker analyses from two ongoing clinical trials
of its lead immuno-oncology single strain Live Biotherapeutic,
MRx0518, in both neoadjuvant and refractory solid tumor settings,
at the European Society for Medical Oncology (ESMO) Congress,
September 16-21, 2021.
“At the core of 4D pharma’s platform is the importance of
understanding the impact of Live Biotherapeutics on human biology
to rationally select and develop candidates, predict and measure
response. These new biomarker data provide us with critical
guidance on the biological and mechanistic impact of MRx0518
therapy in patients with various solid tumors,” said Dr. Alex
Stevenson, Chief Scientific Officer, 4D pharma. “These new findings
indicate the potential to predict patients most likely to respond
to MRx0518 therapy based on tumor biology.”
“Furthermore, the monotherapy data demonstrates that a short
course of MRx0518 treatment is able to positively modulate
prognostic indicators of immunotherapy response,” he added. “We
look forward to utilizing and implementing these important new
findings as we work to progress this novel oncology Live
Biotherapeutic through development towards approval.”
Highlights of the two ESMO 2021 poster presentations:
Baseline biomarkers associated with clinical benefit in
patients with solid tumors refractory to immune checkpoint
inhibitors (ICIs) treated with live biotherapeutic MRx0518 in
combination with pembrolizumab
Presentation Number: 1024P
- Tumor biomarkers were assessed in patients with evaluable
baseline samples (N = 12) in the ongoing Phase I/II study of
MRx0518 in combination with anti-PD-1 immune checkpoint inhibitor
(ICI) Keytruda® (pembrolizumab)
- At baseline, patients who achieved complete response, partial
response or stable disease for at least six months (collectively
‘responders’, N=4) from the combination of MRx0518 with Keytruda®
(pembrolizumab) had significantly greater densities of
CD3+FOXP3+CD8- regulatory T cells (Tregs) and CD3+KI67+
proliferating T cells in tumors at baseline, compared to patients
with progressive disease (PD, N=8), p=0.0381 and p=0.0048,
respectively.
- In addition, significantly lower densities of CD68+ macrophages
at baseline were observed in the tumor microenvironment of
responders compared to patients with progressive disease,
p=0.0303.
These data indicate the potential for MRx0518 to overcome
Treg-mediated acquired resistance to cancer treatment, and presents
a biomarker potentially able to identify patients most likely to
respond to immunotherapy based on MRx0518. Further tumor sample
analysis is ongoing for additional patients recruited into the
study.
Neoadjuvant MRx0518 treatment is associated with significant
gene and metagene signature changes in solid tumours
Presentation Number: 543P
- Gene expression profiling of paired tumor samples pre- and
post-MRx0518 monotherapy across multiple solid tumor types (N=15)
showed that treatment with MRx0518 for two to four weeks was
associated with anti-tumor immune activity including antigen
presentation, innate immune processes, and interferon
response.
- Analysis of paired tumor samples also identified significant
increases in mast cells, Th1, CD8+ T cell, neutrophil, endothelial
cell and inflammatory chemokine metagene signatures following
MRx0518 monotherapy.
- Effects were particularly pronounced in the cohort of breast
cancer patients (N=7), with significant increases observed in total
and activated dendritic cells, CD8+ T cells and cytotoxic cells in
the tumor micro-environment.
- Functional metagene analysis also identified positive changes
in prognostic indicators and metagene signatures predictive of
immunotherapy response in patients with breast cancer, including
inflammatory chemokines, cytotoxicity, lymphoid scores, and the
Tumor Inflammation Signature (TIS)1 - demonstrated to
retrospectively predict clinical benefit of anti-PD-(L)1 ICI
therapy efficacy in various cancer types.
The immune biomarker data from this study of MRx0518, as a
monotherapy dosed over a short period of just two to four weeks,
demonstrates the potent activity of this oral Live Biotherapeutic
directly on the human immune system, and the positive implications
for clinical outcomes. This study is being conducted in
collaboration with Imperial College London.
Both ePosters will be available under the “Posters and
Publications” section of the 4D pharma website at
www.4dpharmaplc.com at 7:30 GMT on Thursday 16th September
2021.
1 Ayers M, et al. J Clin Invest. 2017;127:2930–40
About MRx0518
MRx0518 is single strain Live Biotherapeutic product in
development for the treatment of cancer. It is delivered as an oral
capsule and stimulates the body’s immune system, directing it to
produce cytokines and immune cells that are known to attack
tumours. It is currently being evaluated in three clinical trials
in cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy
study in a variety of solid tumours and is being conducted at
Imperial College (London, UK). MRx0518-I-002 is in combination with
KEYTRUDA® (pembrolizumab) in patients who have previously
progressed on anti PD-1 therapies. The Coordinating Investigator of
the study is at The University of Texas MD Anderson Cancer Center,
Houston, USA, with multiple additional sites in the US. The study
is being conducted in collaboration with MSD, the tradename of
Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is in
combination with preoperative radiotherapy in resectable pancreatic
cancer. A fourth clinical trial, in collaboration with Merck KGaA
and Pfizer Inc., of BAVENCIO® (avelumab) in combination with
MRx0518 as a first-line maintenance therapy for patients with
locally advanced or metastatic urothelial carcinoma that has not
progressed with first-line platinum-containing chemotherapy, is
expected to commence in Q4 2021.
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®, 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® 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.
For more information, refer to https://www.4dpharmaplc.com.
Forward-Looking Statements
This announcement contains "forward-looking statements." All
statements other than statements of historical fact contained in
this announcement, including without limitation statements
regarding the efficacy of Live Biotherapeutics including MRx0518,
their ability to impact cancer treatment outcomes, and the
potential use of biomarkers to predict response are forward-looking
statements within the meaning of Section 27A of the United States
Securities Act of 1933, as amended (the "Securities Act"), and
Section 21E of the United States Securities Exchange Act of 1934,
as amended (the "Exchange Act"). Forward-looking statements are
often identified by the words "believe," "expect," "anticipate,"
"plan," "intend," "foresee," "should," "would," "could," "may,"
"estimate," "outlook" and similar expressions, including the
negative thereof. The absence of these words, however, does not
mean that the statements are not forward-looking. These
forward-looking statements are based on the Company's current
expectations, beliefs and assumptions concerning future
developments and business conditions and their potential effect on
the Company. While management believes that these forward-looking
statements are reasonable as and when made, there can be no
assurance that future developments affecting the Company will be
those that it anticipates.
All of the Company's forward-looking statements involve known
and unknown risks and uncertainties, some of which are significant
or beyond its control, and assumptions that could cause actual
results to differ materially from the Company's historical
experience and its present expectations or projections. The
foregoing factors and the other risks and uncertainties that affect
the Company's business, including the risks relating to the
activity and efficacy of its Live Biotherapeutic drug candidates
including MRx0518, the ability to identify and validate biomarkers
predictive of clinical outcomes, and those additional risks and
uncertainties described the documents filed by the Company with the
US Securities and Exchange Commission ("SEC"), should be carefully
considered. The Company wishes to caution you not to place undue
reliance on any forward-looking statements, which speak only as of
the date hereof. The Company undertakes no obligation to publicly
update or revise any of its forward-looking statements after the
date they are made, whether as a result of new information, future
events or otherwise, except to the extent required by law.
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