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Coya Therapeutics Announces Positive Results of a Double-Blind Study of Subcutaneous Low-Dose Interleukin-2 (LD IL-2) in Alzheimer s Disease (AD) Presented at the Clinical Trials on Alzheimer s Disease Conference (CTAD24) in Madrid (Spain)
HOUSTON, TX, October 29, 2024 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.
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
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.
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 A 42 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
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.
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 A 42: Low CSF A 42 is universally associated with AD, and higher CSF A 42 levels are independently associated with slowing
cognitive impairment and clinical decline. Increases in A 42 may represent a mechanism of potential benefit of intervention. LD IL-2 q4wks treatment significantly improved CSF A 42 levels after the
21-week treatment, compared to the placebo group (p = 0.045). LD IL-2 q2wks treatment did not significantly modify CSF A 42 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 A 42.
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 A 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
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
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.
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.
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,
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
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