A key aspect of Parkinson’s disease (PD)
pathophysiology is decreased systemic regulatory T cell (Treg)
function with associated neuroinflammation in the nigrostriatal
pathway of the brain, including the presence of reactive astrocytes
and microglia that have an initiating and progressing role in
PD;
Subcutaneous injection of COYA 302, an
anti-inflammatory, Treg-enhancing combination biologic (comprising
low dose interleukin-2 and CTLA-4 Ig fusion protein), in an
inflammatory mouse model of PD resulted in significant reductions
in microglia and astrocyte activation in the nigrostriatal pathway
in the brain;
Importantly, study illustrates that peripheral
administration of COYA 302 is directly immunomodulatory in the
brain and associated with significant downregulation of
neuroinflammation
Coya Therapeutics, Inc. (NASDAQ: COYA) (“Coya” or the
“Company”), a clinical-stage biotechnology company developing
biologics intended to enhance regulatory T cell (Treg) function,
announces the direct CNS anti-inflammatory effect of subcutaneously
administered COYA 302 in a preclinical inflammatory associated
mouse model of Parkinson’s Disease (PD).
Coya’s Chief Business Officer and incoming Chief Executive
Officer Arun Swaminathan, Ph.D. stated: “We believe that the
ability of peripherally administered biologics (COYA 302) that
potently and directly ameliorate the inflammatory milieu in the
brain translates to strategies to suppress CNS neuro-inflammation
beyond PD, including other inflammatory mediated neurodegenerative
diseases such as Alzheimer’s disease (AD) and Frontotemporal
Dementia (FTD).”
Parkinson’s disease is characterized by the selective loss of
dopaminergic neurons in brain regions responsible for motor control
(nigrostriatal pathway), while inflammation and immune dysfunction
from the associated loss of systemic Treg function are currently
recognized as critical mediators of disease and subsequent
progression of PD. Targeting the sustained proinflammatory
mechanisms that progress the disease and enhance immunosuppressive
cells, such as Tregs, may have the potential to provide
disease-modifying benefits in patients with PD.
In an inflammatory mouse model of PD, subcutaneous injections of
COYA 302 significantly reduced inflammation and microglial
activation in nigrostriatal brain regions responsible for motor
control (dorsal striatum and substantia nigra). Microglial
activation is an important mediator of PD and plays an important
role in PD pathology and neurodegeneration. Microglial inhibition
may hold promise as a therapeutic strategy to delay the progression
of PD. Additionally, subcutaneous injections of COYA 302 resulted
in reductions in astrocyte numbers and their activation
(astrogliosis) in the nigrostriatal pathway. It is known that
pathogenic astrocyte activation leads to neurodegeneration in PD,
and mitigating its damage may be another therapeutic target. COYA
302’s direct effect in reducing neuroinflammatory constituents
known to drive neurodegeneration is promising and warrants clinical
translation into additional preclinical models and, ultimately,
into patients. The Company anticipates presenting and/or publishing
these data in a peer reviewing setting.
About Parkinson’s Disease
Parkinson’s disease (PD) is the most common movement disorder
and the second most common neurodegenerative disease, affecting
approximately 1% of individuals over the age of 60. Its prevalence
increases significantly with age, and as the global population
continues to age, the incidence of PD is expected to rise further.
The hallmark of PD is the progressive degeneration of dopaminergic
neurons, particularly in the substantia nigra, a region of the
brain integral to the nigrostriatal pathway, which plays a crucial
role in coordinating motor control. This neuronal loss leads to the
characteristic motor symptoms of PD, such as bradykinesia,
rigidity, and tremors, while patients also exhibit non-motor
manifestations, such as cognitive decline, mood disturbances, and
sleep disorders.
While the exact cause of the dopaminergic neuron loss is not
fully understood, growing evidence highlights chronic
neuroinflammation and immune dysfunction as central drivers of PD
pathogenesis and progression. A key aspect of PD pathophysiology is
neuroinflammation in the nigrostriatal pathway, including the
presence of reactive astrocytes. This neuroinflammation has long
been considered a downstream response to the death of dopaminergic
neurons. However, increased evidence suggests that astrocytes have
an initiating role in PD pathophysiology. Regulatory T cells
(Tregs), a subset of T cells responsible for maintaining immune
homeostasis and preventing excessive immune responses, are
decreased and impaired in PD patients and preclinical models.
Subsequently, chronic pro-inflammatory immune cell activation,
oxidative stress, and mitochondrial dysfunction all contribute to
neuronal damage. The combination of targeting the chronic,
proinflammatory activation and enhancing the Treg immunosuppressive
function offers promising therapeutic potential for a
disease-modifying therapy that could effectively alter the course
of the disease, reduce neuronal loss, and improve patient
outcomes.
References
1. Kouli, Torsney, and Kuanl. Chapter 1 - Parkinson’s Disease:
Etiology, Neuropathology, and Pathogenesis; Parkinson’s Disease: Pathogenesis and Clinical
Aspects, Codon Publications, 2018
2. Booth, Hirst, and Wade-Martins. The Role of Astrocyte
Dysfunction in Parkinson’s Disease Pathogenesis; Trends in
Neuroscience, 2017 June, 40(6): 358-370
About COYA 302
COYA 302 is an investigational and proprietary biologic
combination therapy with a dual immunomodulatory mechanism of
action intended to enhance the anti-inflammatory function of
regulatory T cells (Tregs) and suppress the inflammation produced
by activated monocytes and macrophages. COYA 302 is comprised of
proprietary low dose interleukin-2 (LD IL-2) and CTLA4-Ig fusion
protein and is being developed for subcutaneous administration for
the treatment of patients with ALS, AD, FTD, and PD. These
mechanisms may have additive or synergistic effects.
In February of 2023, Coya announced results from a
proof-of-concept, open-label clinical study evaluating commercially
available LD IL-2 and CTLA4-Ig fusion protein in a small cohort of
patients with ALS conducted at the Houston Methodist Research
Institute (Houston, Texas) by Stanley Appel, M.D., Jason Thonhoff,
M.D., Ph.D., and David Beers, Ph.D. This study was the
first-of-its-kind evaluating this dual-mechanism immunotherapy for
the treatment of ALS. Patients in the study received
investigational treatment for 48 consecutive weeks and were
evaluated for safety and tolerability, Treg function, serum
biomarkers of oxidative stress and inflammation, and clinical
functioning as measured by the ALSFRS-R scale.
During the 48-week treatment period, the therapy was well
tolerated. The most common adverse event was mild injection-site
reactions. No patient discontinued the study, and no deaths or
other serious adverse events were reported.
Patients' disease progression was measured using the ALSFRS-R
scale, a validated rating tool for monitoring the progression of
disability in patients with ALS. The mean (±SD) ALSFRS-R scores at
week 24 (33.75 ±3.3) and week 48 (32 ±7.8) after initiation of
treatment were not statistically different compared to the ALSFRS-R
score at baseline (33.5 ±5.9), suggesting significant amelioration
in the progression of the disease over the 48-week treatment
period.
Treg suppressive function, expressed as percentage of inhibition
of proinflammatory T cell proliferation, showed a statistically
significant increase over the course of the treatment period and
was significantly reduced at the end of the 8-week washout
post-treatment period. Treg suppressive function at 24 weeks (79.9
±9.6) and 48 weeks (89.5 ±4.1) were significantly higher compared
to baseline (62.1 ±8.1) (p<0.01), suggesting enhanced and
durable Treg suppressive function over the course of treatment. In
contrast, Treg suppressive function (mean ±SD) was significantly
decreased at the end of the 8-week washout period compared to
end-of-treatment at week 48 (70.3 ±8.1 vs. 89.5 ±4.1, p
<0.05).
The study also evaluated serum biomarkers of inflammation,
oxidative stress, and lipid peroxides. The available data up to 16
weeks after initiation of treatment suggest a decrease in these
biomarker levels, which is consistent with the observed enhancement
of Treg function. The evaluation of the full biomarker data is
ongoing.
COYA 302 is an investigational product not yet approved by the
FDA or any other regulatory agency.
About Coya Therapeutics, Inc.
Headquartered in Houston, TX, Coya Therapeutics, Inc. (Nasdaq:
COYA) is a clinical-stage biotechnology company developing
proprietary treatments focused on the biology and potential
therapeutic advantages of regulatory T cells (“Tregs”) to target
systemic inflammation and neuroinflammation. Dysfunctional Tregs
underlie numerous conditions, including neurodegenerative,
metabolic, and autoimmune diseases, and this cellular dysfunction
may lead to sustained inflammation and oxidative stress resulting
in lack of homeostasis of the immune system.
Coya’s investigational product candidate pipeline leverages
multiple therapeutic modalities aimed at restoring the
anti-inflammatory and immunomodulatory functions of Tregs. Coya’s
therapeutic platforms include Treg-enhancing biologics,
Treg-derived exosomes, and autologous Treg cell therapy.
COYA 302 – the Company’s lead biologic investigational product
or “Pipeline in a Product” – is a proprietary combination of COYA
301 (Coya’s proprietary LD IL-2) and CTLA4-Ig for subcutaneous
administration with a unique dual mechanism of action that is now
being developed for the treatment of Amyotrophic Lateral Sclerosis,
Frontotemporal Dementia, Parkinson’s Disease, and Alzheimer’s
Disease. Its multi-targeted approach enhances the number and
anti-inflammatory function of Tregs and simultaneously lowers the
expression of activated microglia and the secretion of
pro-inflammatory mediators. This synergistic mechanism may lead to
the re-establishment of immune balance and amelioration of
inflammation in a sustained and durable manner that may not be
achieved by either low-dose IL-2 or CTLA4-Ig alone.
For more information about Coya, please visit
www.coyatherapeutics.com
Forward-Looking Statements
This press release contains “forward-looking” statements that
are based on our management’s beliefs and assumptions and on
information currently available to management. Forward-looking
statements include all statements other than statements of
historical fact contained in this presentation, including
information concerning our current and future financial
performance, business plans and objectives, current and future
clinical and preclinical development activities, timing and success
of our ongoing and planned clinical trials and related data, the
timing of announcements, updates and results of our clinical trials
and related data, our ability to obtain and maintain regulatory
approval, the potential therapeutic benefits and economic value of
our product candidates, competitive position, industry environment
and potential market opportunities. The words “believe,” “may,”
“will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,”
and similar expressions are intended to identify forward-looking
statements.
Forward-looking statements are subject to known and unknown
risks, uncertainties, assumptions and other factors including, but
not limited to, those related to risks associated with the impact
of COVID-19; the success, cost and timing of our product candidate
development activities and ongoing and planned clinical trials; our
plans to develop and commercialize targeted therapeutics; the
progress of patient enrollment and dosing in our preclinical or
clinical trials; the ability of our product candidates to achieve
applicable endpoints in the clinical trials; the safety profile of
our product candidates; the potential for data from our clinical
trials to support a marketing application, as well as the timing of
these events; our ability to obtain funding for our operations;
development and commercialization of our product candidates; the
timing of and our ability to obtain and maintain regulatory
approvals; the rate and degree of market acceptance and clinical
utility of our product candidates; the size and growth potential of
the markets for our product candidates, and our ability to serve
those markets; our commercialization, marketing and manufacturing
capabilities and strategy; future agreements with third parties in
connection with the commercialization of our product candidates;
our expectations regarding our ability to obtain and maintain
intellectual property protection; our dependence on third party
manufacturers; the success of competing therapies or products that
are or may become available; our ability to attract and retain key
scientific or management personnel; our ability to identify
additional product candidates with significant commercial potential
consistent with our commercial objectives; and our estimates
regarding expenses, future revenue, capital requirements and needs
for additional financing.
We have based these forward-looking statements largely on our
current expectations and projections about future events and trends
that we believe may affect our financial condition, results of
operations, business strategy, short-term and long-term business
operations and objectives, and financial needs. Moreover, we
operate in a very competitive and rapidly changing environment, and
new risks may emerge from time to time. It is not possible for our
management to predict all risks, nor can we assess the impact of
all factors on our business or the extent to which any factor, or
combination of factors, may cause actual results to differ
materially from those contained in any forward-looking statements
we may make. In light of these risks, uncertainties and
assumptions, the forward-looking events and circumstances discussed
herein may not occur and actual results could differ materially and
adversely from those anticipated or implied in the forward-looking
statements. Although our management believes that the expectations
reflected in our forward-looking statements are reasonable, we
cannot guarantee that the future results, levels of activity,
performance or events and circumstances described in the
forward-looking statements will be achieved or occur. We undertake
no obligation to publicly update any forward-looking statements,
whether written or oral, that may be made from time to time,
whether as a result of new information, future developments or
otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20240916839101/en/
Investor Contact David
Snyder, CFO david@coyatherapeutics.com CORE IR Bret Shapiro
brets@coreir.com 561-479-8566 Media
Contacts For Coya Therapeutics: Kati Waldenburg
media@coyatherapeutics.com 212-655-0924
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