RCS - Argent Biopharma Ltd - CimetrA - Technical Overview

Argent BioPharmaAnnouncement

09/09/2024 07:00

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RNS Number : 3914D  Argent Biopharma Limited  09 September 2024

 

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:

 

 Argent BioPharma                                             Argent BioPharma

 Roby Zomer                                                   Rowan Harland

 CEO & Managing Director                                      Company Secretary

 +61 8 6555 2950                                              +61 8 6555 2950

 info@argentbiopharma.com (mailto:info@argentbiopharma.com)   info@argentbiopharma.co (mailto:info@argentbiopharma.co.uk) m

 

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.

 

Follow us through our social media channels:

LinkedIn: Argent BioPharma

Twitter: @ArgentBioPharma

Facebook: Argent BioPharma

 

 

 

 

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