9
September 2024
Argent BioPharma
Ltd.
(Argent BioPharma or the Company)
CimetrA®
CimetrA® is a compounded
multi-targeted anti-inflammatory and immunomodulatory formulation.
It is designed to address severe inflammatory responses by
specifically targeting multiple key cytokines and multiple
inflammatory pathways involved in immune system
regulation.
CimetrA® has undergone several
formulation adaptations based on the data from stability and
preclinical studies. Its precursor, ArtemiC, was initially
developed and tested in preclinical and clinical studies, providing
valuable insights that guide the ongoing development of CimetrA®.
In this overview, we will focus solely on CimetrA®, without further
reference to ArtemiC, as the relevant findings have been integrated
into the ongoing development of CimetrA®.
Development and Reformulation
·
Initial Discovery
(April 2020):
o CimetrA® was first developed in April 2020 with a complex
initial formula aimed at treating anti-infective, anti-viral, and
anti-inflammatory conditions. Through various clinical and
preclinical trials, researchers were able to determine the safety
profile and efficacy of the drug while also establishing an
understanding of its mechanism of action.
·
Reformulation
(2021, 2022):
o In 2021
Artemisinin was initially included
in the CimetrA® formulation for its well-known anti-viral
properties. However, over the course of its development, it was
discovered that Artemisinin did not significantly contribute to the
overall efficacy of CimetrA® in treating inflammatory conditions,
leading to its removal from the formulation that same year. These
changes reflect ongoing efforts to optimize CimetrA®'s
effectiveness and stability as the product continues to
evolve.
o The
updated CimetrA® now primarily relies on two active ingredients.
These components have demonstrated substantial effects in reducing
inflammation and modulating the immune response. This reformulation
was likely driven by clinical trial results indicating that the
combination of Curcumin and Boswellia serrata alone was sufficient
to achieve the desired therapeutic outcomes.
Why
CimetrA® is Multi-Targeted
CimetrA® is considered
multi-targeted because it interacts with and modulates several
critical immune response elements rather than focusing on a single
pathway. This approach allows CimetrA® to exert a broader and more
comprehensive effect on inflammation, making it effective in
treating complex inflammatory conditions.
1. IL-32 Pathway
Inhibition:
o CimetrA® inhibits the expression of IL-32 mRNA, a cytokine that plays a
central role in triggering inflammatory pathways such as
NF-κB and p38 MAP kinase. These pathways are
responsible for the production of other pro-inflammatory cytokines
like TNF-α and IL-6. By affecting the expression
of IL-32, CimetrA® could aid in reduced B activation of these
downstream pathways, effectively lowering inflammation across
multiple fronts.
2. HO-1 Pathway Activation:
o CimetrA® upregulates Heme
Oxygenase-1 (HO-1), an enzyme known for its antioxidant and
anti-inflammatory properties. HO-1 breaks down heme into
biliverdin, carbon monoxide, and free iron, substances that help
protect cells from oxidative stress and reduce inflammation. This
pathway adds another layer of protection by mitigating the effects
of oxidative damage and chronic inflammation.
3. Modulation of Cytokine
Production:
o CimetrA® effectively reduces the production of several key
cytokines, including IL-1α, IL-1β , IL-6, TNF-α, and IFN-γ which are
central to the inflammatory response. This modulation helps to
prevent excessive immune responses, such as cytokine storms, which
can lead to significant tissue damage and severe
complications.
Mechanism of Action
Multi-Targeted Approach: CimetrA®'s ability to simultaneously target multiple
inflammatory pathways makes it a versatile and effective treatment
for managing complex immune responses.
Therapeutic Application
CimetrA® is used in the treatment of
inflammatory conditions where traditional therapies may be
inadequate. Its multi-targeted action allows it to address complex
immune responses, making it a valuable tool in managing diseases
characterized by severe inflammation and immune
dysregulation.
Clinical Pathway
· Early Development and
Preclinical Studies (Early 2020):
o Extensive preclinical studies were conducted to assess the
safety, efficacy, and pharmacokinetics of CimetrA®, focusing on its
ability to modulate immune responses and manage cytokine storms.
These studies included experiments conducted in vitro on isolated
human mononuclear cells and in vivo on mice and rats. The findings
were crucial in demonstrating the potential of CimetrA® to reduce
inflammation and prevent severe immune reactions, such as cytokine
storms.
· Clinical Trials and
Development:
o Phase II Clinical Trial
(2020):
A pivotal Phase II clinical trial
was conducted in 2020 to evaluate CimetrA®'s efficacy in patients
hospitalized due to moderate pulmonary inflammatory conditions.
This double-blind, placebo-controlled trial showed that patients
treated with CimetrA® had significantly better clinical outcomes,
with none requiring additional oxygen or intensive care.
o Phase IIb Dose-Finding
Study:
Following the success of the Phase
II trial, a Phase IIb study was conducted to identify the optimal
dosing regimen for CimetrA®. This study was essential in refining
the treatment protocol to maximize efficacy and minimize side
effects.
o Open-Label
Studies:
Additional open-label studies,
including those on patients with long-lasting inflammatory
conditions, provided valuable real-world data supporting CimetrA®'s
therapeutic benefits in managing the severity of clinical symptoms
associated with excessive immune stimulation. These studies
contributed to the ongoing assessment of the product's safety and
effectiveness.
o Safety study in
pigs:
A preclinical study involving
healthy pigs was carried out to evaluate the safety of CimetrA® at
doses intended for clinical use. Pigs were selected due to their
physiological similarities to humans, making this study a critical
step in evaluating the effects of CimetrA® on human
systems.
· Transition and Rebranding to
CimetrA® (2021, 2022):
o Reformulation and
Rebranding:
In 2021/2022, the formulation was
refined by removing Artemisinin due to its minimal contribution to
overall efficacy and stability. The product was rebranded as
CimetrA® and optimized with two primary active components. This
change marked a significant shift towards improving the product's
anti-inflammatory and immunomodulatory effects.
o Preclinical and Clinical
Studies (2021-2022):
CimetrA® continued to undergo
various preclinical and clinical studies. These included the
evaluation of its efficacy in reducing cytokine production in
severe inflammatory responses. The studies reinforced the safety
and effectiveness of the rebranded formulation, confirming its
potential in broader therapeutic applications beyond its initial
use.
· Phase III Clinical Trial
(2021):
A Phase III clinical trial was
initiated but later stopped. The trial was halted due to the
company's ongoing communication with the FDA to identify the
fastest and most effective pathway to marketing authorization. This
process includes potential changes to the Phase III trial, and as
such, the trial was paused until the FDA dialogue is
completed.
· Planned Preclinical Studies
(2024-):
A series of preclinical studies to
further evaluate CimetrA®'s efficacy for new indications is set to
begin before the end of the year. These studies, conducted in
collaboration with a renowned German institute, will include ex
vivo testing across various indications and in vivo testing on a
complex animal model.
-Ends-
Authorised for release by the board of directors, for further
information please contact:
About Argent
BioPharma
Argent BioPharma Limited (the
"Company") (ASX: RGT; LSE:
RGT; OTCQB: RGTLF) an innovative multidisciplinary drug development
Company within the biopharmaceutical sector. The Company
focuses on multidisciplinary methods with Nanotechnology,
developing multi-target therapies for comprehensive disease
management, especially concerning the central nervous system
("CNS") and Immunology
treatments.
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