Pharma Equity Group’s subsidiary, Reponex Pharmaceuticals A/S, reports highly positive final results from the phase-2 clinical trial of the company’s patented drug candidate RNX-051.
April 05 2024 - 5:22AM
UK Regulatory
Pharma Equity Group’s subsidiary, Reponex Pharmaceuticals A/S,
reports highly positive final results from the phase-2 clinical
trial of the company’s patented drug candidate RNX-051.
5 April 2024
Company Announcement No. 11
Pharma Equity Group’s subsidiary,
Reponex Pharmaceuticals A/S, reports highly positive final results
from the phase-2 clinical trial of the company’s patented drug
candidate RNX-051.
Reponex Pharmaceuticals A/S (Reponex) today
announced positive final results from the phase-2 clinical
proof-of-concept trial of the drug candidate RNX-051, the MEFO
trial, based on received high level summary from the Company’s
clinical site.
Reponex’s MEFO-trial
This concerns the treatment of patients with right-sided colon
cancer and right-sided colon polyps/adenomas (precursors of cancer)
with the Company’s drug candidate RNX-051. The company’s clinical
collaborators who have performed the trial report the
following:
Background
Patients with precursor lesions to cancer in the colon (adenomas)
harbor a different gut microbiota than healthy controls. Distinct
bacteria have been found to influence the bowel lining by promoting
chronic inflammation and through interaction with molecular
mechanisms in the bowel cells that may lead to bowel cancer. A
central mechanism of the bacteria with cancer promoting abilities
is to produce a biofilm lining the inner surface of the bowel
wall.
In patients where the cancer has already
developed, it is known that distinct bacteria such as
Fusobacterium nucleatum and Bacteroides fragilis
shift the immune system within the tumor leading to a greater risk
of metastatic spread of the cancer. The mechanisms are complex but
mediated through reducing the function of immune cells that are
actively killing cancer cells.
Rationale
Administering the two antibiotics fosfomycin and metronidazole
(constituents of RNX-051) with distinct properties ensuring an
effect both on the colon lining and inside the cancer through local
administration may change the milieu leading to a reduced risk of
adenoma generation and improved sensitivity to immune cells or
therapies that modulate the immune system, such as immune
check-point inhibitors. The MEFO trial consisted of two arms: the
first in patients with adenomas (the “adenoma arm”) and second in
patients with cancers in the right side of the bowel (the “cancer
arm”). A major aim was to change the biofilm in the “adenoma arm”
and improve the tumor-related bacterial composition in the “cancer
arm”. In both arms there was a focus on the modulation of the
immune cells in a positive way to increase their ability to kill
precursor or cancer cells.
Protocol
Twelve patients and ten patients were treated in the respective
arms of the trials with RNX-051 given in a muco-adhesive spray and
the adenomas or tumor were removed approximately one week after the
intervention. Through advanced microscopy analyses targeting
certain bacteria and certain cells of the tumor microenvironment,
and advanced immune analyses including genomic analyses of both the
bacteria and the precursor and cancer lesions, an in-depth overall
picture of the precursor lesions and the cancer before and after
treatment was obtained.
Results
In the adenoma arm, the main goal of the study, to demonstrate an
impact on the bacterial biomass, was reached, with a massive
reduction in the biofilm of the bowel lining (more than 30-fold
reduction) one week after the treatment, from a mean of 0.003% to
0.0001% of bacterial biomass (p=0.025). An impact on the occurrence
of specific immune-cells known to be crucial in the immune response
against cancer was shown (macrophages and T-cells). For
macrophages, the density was 2.2% in non-treated adenomas and 3.4%
in treated adenomas (p=0.030), and for CD3 T-cells, the density was
524 cells/mm2 in non-treated adenomas and 727
cells/mm2 in treated adenomas (p=0.018). In the
metagenome sequencing to assess the diversity of bacteria and the
specific composition of bacteria before and after treatment, there
was no reduction in the diversity of bacteria, while there was an
increase of the genus Bacteroides (median 6.9% vs 10.8% ,
p=0.016), a commensal gut bacterium containing both anti- and
pro-inflammatory species.
In the cancer arm, for patients with a high
content of bacterial biofilm, there was a statistically significant
reduction of biofilm in the tumor periphery from a mean of 0.255%
to 0.013% of bacterial biomass (p=0.025). At the same time, a shift
in the balance of immune cells in the tumor core could be seen,
resulting in an increase in the ratio of T-cells that are
particularly active in promoting tumor cell death, from a mean 0.30
CD8/CD3 ratio to a mean ratio of 1.19 (p=0.016). In the metagenome
sequencing to assess the diversity of bacteria and the specific
composition of bacteria before and after treatment, a clear and
statistically significant effect was seen. The RNX-051 application
drastically reduced or eliminated the cancer-promoting
Fusobacterium nucleatum (median 15.2% to 0%, p=0.008) and
increased the cancer-protecting Lactobacillales (median 0.23% to
2.72% p=0.023) in the tumor center without reducing the diversity
of the mucosa-associated gut microbiota.
Conclusions
Based on the findings of the MEFO trial, there seems to be a clear
path for establishing whether the treatment with RNX-051 as a
single and even repeated dose in patients with adenomas in the
bowel will lead to adenoma prevention.
For patients with colon cancer, it seems relevant to investigate
whether the shift in the composition of immune cells (increase) and
cancer-promoting bacteria (reduction) can result in positive
effects in a larger cohort of patients and whether combination
trials with RNX-051 plus immune therapy may also provide benefits
for the patients with bowel cancer.
Reponex management
concludes that its patented medicinal product RNX-051
appears to be highly effective for its intended purpose. Just a
single local application drastically reduces tumor-associated
biofilm and can even totally eliminate the cancer-promoting
Fusobacterium nucleatum in the tumor at one week after the
treatment.
Contact person – Investor
Relations
On the Company’s website
www.pharmaequitygroup.com further information and all published
announcements can be found.
Inquiries regarding relations with investors and
the stock market can be directed to:
Thomas Kaas Selsø, CEO, Phone: +45 4022 2114 E-mail:
investor@pharmaequitygroup.com
About Pharma Equity Group
A/S
Pharma Equity Group, a listed company on the
Nasdaq Copenhagen stock exchange, is fully dedicated to advancing
the medical projects of its subsidiary, Reponex Pharmaceuticals
A/S. With an unwavering focus on healthcare, Pharma Equity Group's
primary objective is to bring significant value to Reponex
Pharmaceuticals' medical projects.
The company is committed to providing
extensive support, resources, and expertise to drive the
development and success of these projects. As a strategic partner,
Pharma Equity Group works closely with Reponex Pharmaceuticals,
prioritizing the advancement of innovative medical solutions and
breakthrough therapies. Every effort is currently directed towards
ensuring the utmost success and impact of Reponex Pharmaceuticals'
medical projects, with an unwavering dedication to improving global
healthcare outcomes. Only when the full potential of Reponex
Pharmaceuticals has been unfolded is the intention to explore
opportunities to invest in other companies. This approach ensures a
strong commitment to the current medical projects and their
development, while – on the longer term – remaining open to new
strategic investments for continuous growth.
- 2024 04 05 - Announcement no. 11 - UK
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