- Study met Primary and Secondary Endpoints for
Safety and Regulatory T cell (Treg) Cell Population Enhancement,
respectively, with no off-target effects on T effector lymphocytes,
providing further evidence of target engagement
- Exploratory Endpoints demonstrated cognitive
stabilization on treatment vs. cognitive declines on placebo for LD
IL-2 dosing every 4 weeks (LD IL-2 q4wks), which was associated
with significant improvement in cerebrospinal fluid (CSF) soluble
Aβ42 levels and stabilized CSF Neurofilament Light Chain (NfL)
- Study supports and increases confidence in
Treg modulation strategies in neurodegenerative conditions and in
advancing LD IL-2 q4wks and LD IL-2 q4wks combination strategies
(i.e. COYA 302) in AD and other related diseases
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 that results from the placebo-controlled Phase 2 clinical
trial of LD IL-2 in patients with mild to moderate Alzheimer's
Disease were announced today at the 17th Clinical Trials on
Alzheimer’s Disease Conference (CTAD24) in Madrid, Spain. The study
was led by Dr. Alireza Faridar and Dr. Stanley Appel from the
Houston Methodist Research Institute. Dr. Appel is a member of
Coya’s Scientific Advisory Board. The study received funding from
the Alzheimer's Association, the Gates Foundation, and the National
Institute on Aging, with additional support from Coya. The
presentation summarizing the clinical results is available for
viewing here.
“We want to express our gratitude to the investigators for this
study. We believe this trial strongly supports and adds further
validation of Coya’s approach in modulating Treg function as a
platform to address neurodegenerative diseases,” said Arun
Swaminathan, Ph.D., incoming CEO of Coya. “These monotherapy
treatment results increase our confidence that combinations of COYA
301, our proprietary LD IL-2, with other drug targets have strong
potential in treating Alzheimer's Disease. In addition, this data
on LD IL-2 alone provides additional confidence in COYA 302, our
proprietary combination of LD IL-2 and cytotoxic T
lymphocyte-associated antigen 4 immunoglobulin fusion protein
(CTLA4-Ig) in amyotrophic lateral sclerosis (ALS) and
frontotemporal dementia (FTD) based on increased and more durable
Treg suppressive function observed with the combination in patients
with ALS.”
Study Design:
The investigator-initiated, randomized, double-blind,
placebo-controlled Phase 2 trial evaluated two dosing regimens of
subcutaneous low-dose interleukin-2 in 38 participants with
Alzheimer’s disease that were between the ages of 50 to 86 and had
Mini-Mental State Examination (MMSE) scores ranging from 12 to
26.
Of the 38 total participants, 22 were randomized in a 1:1 ratio
to receive either 5 days of LD IL-2 (106 IU/day) (LD IL-2 q4wks) or
placebo every 4 weeks for 21 weeks. An additional 16 participants
were randomized in a 2:1 ratio to receive 5-day cycles of LD IL-2
every 2 weeks (LD IL-2 q2wks) or placebo for the same 21-week
duration. All participants were monitored for 9 weeks
post-treatment, resulting in a total study period of 30 weeks.
Demographics and baseline disease characteristics were comparable
among the treatment groups.
The primary endpoint was the incidence and severity of adverse
events (AEs), with the secondary endpoint evaluating changes in
Tregs. Exploratory endpoints assessed changes in cerebrospinal
fluid (CSF), AD-related biomarkers, and cognitive status.
Study Results:
The study successfully met its primary and secondary endpoints,
demonstrating that treatment with low-dose interleukin-2 is safe
and well-tolerated in patients with Alzheimer’s disease. Notably,
LD IL-2 showed targeted biological activity, evidenced by a
significant expansion of regulatory T cell populations in the LD
IL-2 q4wks group without any off-target effects on other peripheral
lymphocytes. Additionally, the q4wks regimen led to significant
improvements (defined by increased levels) in cerebrospinal fluid
(CSF)-soluble Aβ42 levels, an indicator of amyloid pathology, and
showed a promising trend in stabilizing cognitive function, with a
clinically meaningful 4.93-point improvement1 in the ADAS-Cog14
score compared to placebo.
In contrast, the q2wks group, representing the higher total dose
cohort, did not exhibit benefits in exploratory endpoints,
underscoring the importance of appropriate IL-2 dosing for
maintaining Treg functionality and its associated effects on CSF
biomarkers and cognitive outcomes. LD IL-2 q2wks dosing also
resulted in a reduction of Foxp3 expression, a critical marker of
Treg functionality (a lower level or loss of Foxp3 expression is
associated with unstable/dysfunctional Tregs). While these unstable
Tregs continue to show suppressive immune response in vitro, they
may lose their immunomodulatory functions in vivo, potentially
explaining the dose impact on Treg populations and associated
exploratory endpoints. As a result of these data, the Company will
likely advance LD IL-2 q4wks.
Primary Endpoint (Safety and
Tolerability): All patients completed the 21-week
treatment phase. The proportion of patients experiencing adverse
events (AEs) was similar between the LD IL-2 treatment groups and
the placebo group, with no serious AEs or deaths reported. The most
common AEs in the LD IL-2 groups included mild erythema at the
injection site and a slight increase in eosinophil counts.
Secondary Endpoint (Treg Cell
Populations): There was a significant increase (p <
0.05) in the percentage of CD4+ FOXP3+CD25 high Tregs, mean
fluorescence intensity (MFI) of Foxp3, Treg CD25 MFI, and Treg
suppression of T responders following both dosing regimens of LD
IL-2 treatment compared to placebo. Notably, the LD IL-2 q4wks
treatment group showed greater enhancement in both Treg numbers and
Foxp3 MFI compared to the q2wks group. The loss of Foxp3 expression
in the q2wks group (back to baseline levels equivalent to placebo)
indicated that higher IL-2 dosing may compromise Treg
functionality. Repeated stimulation of Tregs without sufficient
rest periods has been reported to result in exhausted and unstable
Treg populations2. Published studies also suggest an inverse
relationship between IL-2 dose and Treg functionality3,4.
- For patients with mild AD, a change of +3 on the ADAS-Cog has
been described as clinically meaningful to assess worsening (Muir
et al., Alzheimer’s Dement 2024; 20:3352–3363).
- Hoffmann, et al. Loss of FOXP3 expression in natural human
CD4+CD25+ regulatory T cells upon repetitive in vitro stimulation.
Eur J Immunol 2009; 39 (4): 1088-1097.
- Gao et al., Dynamically modeling the effective range of IL-2
dosage in the treatment of systemic lupus erythematosus. iScience
2022; 25: 104911
- Moon B-I., et al., Functional Modulation of Regulatory T Cells
by IL-2. PLoS ONE 2015; 10(11)
Exploratory Endpoint (Cognitive
Function & Cerebrospinal Fluid (CSF)
Biomarkers):
Although not powered for significance, the analyses of
exploratory endpoints also showed encouraging results.
Cognitive Function: The Alzheimer’s Disease Assessment
Scale–Cognitive Subscale (ADAS-Cog14) scores on day 148 showed a
slight improvement following LD IL-2 q4wks administration (change
from baseline: -0.450), vs. placebo, which worsened 4.480 from
baseline, demonstrating a clinically meaningful difference of 4.93
points (P=0.061). This cognitive effect was not observed in the LD
IL-2 q2wks administration, which demonstrated a similar decline as
placebo.
Stabilization of ADCS-CGIC (Alzheimer's Disease Assessment Scale
– Cognitive Subscale) scores was observed in both the IL-2 q4wks
and IL-2 q2wks groups on day 148 compared to the placebo arm, which
declined from baseline.
The change from baseline in the Clinical Dementia Rating Scale
Sum of Boxes (CDR-SOB) on Day 148 was 1.401 in the LD IL-2 q4wks
group, 1.976 in the LD IL-2 q2wks group, and 1.893 in the placebo
group, suggesting a 27% slower decline in CDR-SOB scores following
LD IL-2 q4wks treatment compared to the placebo group. These
findings suggest that LD IL-2 q4wks may be an optimal dose for
cognitive effects in mild to moderate AD, which was the dose
associated with a robust and sustained increase in Treg populations
along with enhanced expression of the IL-2 receptor, CD25, and the
Treg transcription factor, FoxP3. Furthermore, the cognitive effect
of this dose was associated with significant improvements in AD
pathology in the CSF and stabilization of CSF inflammatory
markers.
CSF Aβ42: Low CSF Aβ42 is universally associated with AD,
and higher CSF Aβ42 levels are independently associated with
slowing cognitive impairment and clinical decline. Increases in
Aβ42 may represent a mechanism of potential benefit of
intervention. LD IL-2 q4wks treatment significantly improved CSF
Aβ42 levels after the 21-week treatment, compared to the placebo
group (p = 0.045). LD IL-2 q2wks treatment did not significantly
modify CSF Aβ42 levels. These data further suggest the
dose-dependent effect of LD IL-2 on Treg cell populations (i.e.
FOXP3) is associated with effects on CSF Aβ42.
CSF Neurofilament Light Chain (NfL): NfL is increasingly
recognized as a promising biomarker for neurodegeneration
(neuronal/axonal degeneration) in AD. Residing predominantly within
myelinated axons, NfL is a cytoskeletal protein that plays a role
in maintaining neuronal structural integrity and axonal caliber.
Neuronal damage in neurodegenerative diseases releases NfL into the
extracellular space and eventually into the CSF, resulting in
higher CSF NfL levels in AD.
CSF NfL levels remained stable following LD IL-2 q4wks
administration and almost reached statistical significance vs.
placebo (which increased by 217.3pg/mL) (p=0.060). CSF NfL
increased by 148.0 pg/mL in the LD IL-2 q2wks arm. These data
suggest the dose-dependent effect of LD IL-2 on Treg cell
populations (i.e. FOXP3) is associated with effects on CSF NfL.
CSF Glial Fibrillary Acidic Protein (GFAP): GFAP is an
astrocytic cytoskeleton intermediate filament protein. GFAP is a
marker of astrogliosis, which is the abnormal activation and
proliferation of astrocytes. Astrogliosis is associated with Aβ
plaques in the prodromal stages of AD.
CSF GFAP levels showed a slight improvement following LD IL-2
q4wks administration (change from baseline: -214.1 pg/mL) and
remained almost stable in the LD IL-2 q2wks group (change from
baseline: 17.4 pg/mL), but increased by 1548.99 pg/mL in the
placebo group.
About Alzheimer’s Disease
Alzheimer's disease is the most common cause of dementia, a
general term for memory loss and other cognitive abilities serious
enough to interfere with daily life. Alzheimer's disease accounts
for up to 80% of dementia cases, affecting an estimated 5.7 million
Americans. In more than 90% of people with Alzheimer’s, symptoms do
not appear until after age 60. The incidence of the disease
increases with age and doubles every 5 years beyond age 65.
Alzheimer's is a progressive disease, where dementia symptoms
gradually worsen over a number of years. In its early stages,
memory loss is mild, but with late-stage Alzheimer's, individuals
lose the ability to carry on a conversation and respond to their
environment. It is the sixth leading cause of death among all
adults and the fifth leading cause for those aged 65 or older. On
average, a person with Alzheimer's lives 4 to 8 years after
diagnosis but can live as long as 20 years, depending on other
factors.1,2
- Alzheimer’s Association (www.alz.org)
- Centers for Disease Control and Prevention (www.cdc.gov)
About COYA 301
COYA 301 is the company’s proprietary investigational low-dose
interleukin-2 (IL-2) intended to enhance the anti-inflammatory
function of regulatory T cells (Tregs) and is designed for
subcutaneous administration. COYA 301 is an investigational product
not yet approved by the FDA or any other regulatory agency.
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 cytotoxic T
lymphocyte-associated antigen 4 immunoglobulin fusion protein
(CTLA-4 Ig) and is being developed for subcutaneous administration
for the treatment of patients with ALS, FTD, and Parkinson’s
Diseases (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 CTLA-4 Ig 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 to evaluate
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 Revised
Amyotrophic Lateral Sclerosis Functional Rating Scale (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 a 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 a 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20241029490704/en/
Investors David Snyder, CFO
david@coyatherapeutics.com
CORE IR Bret Shapiro brets@coreir.com 561-479-8566
Media For Coya Therapeutics:
Kati Waldenburg media@coyatherapeutics.com 212-655-0924
Grafico Azioni Coya Therapeutics (NASDAQ:COYA)
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