Coya Therapeutics Reports Statistically Significant Improvement of Inflammatory Blood Markers in Patients with Alzheimer’s Disease Following Monthly Dosing with Low-Dose IL-2, Further Supporting Clinical Development
Coya Therapeutics (NASDAQ: COYA) reported positive results from a Phase 2 study of low-dose IL-2 (LD IL-2) in Alzheimer's disease patients. The 21-week, double-blind, placebo-controlled trial demonstrated statistically significant improvements in inflammatory blood markers with monthly dosing.
Key findings include reduced levels of proinflammatory markers CCL2 (p<0.05) and IL-15 (p<0.001), increased anti-inflammatory cytokine IL-4 (p<0.01), and improved beta amyloid 42 clearance. Patients receiving monthly LD IL-2 showed a 4.93-point improvement in ADAS-Cog score compared to placebo.
The study involved 38 participants aged 50-86 with Alzheimer's disease. Monthly dosing proved more effective than biweekly administration. The treatment was well-tolerated with no serious adverse events reported. The comprehensive data set will be presented throughout 2025.
Coya Therapeutics (NASDAQ: COYA) ha riportato risultati positivi da uno studio di Fase 2 sull'IL-2 a basso dosaggio (LD IL-2) in pazienti affetti da malattia di Alzheimer. Il trial, della durata di 21 settimane, in doppio cieco e controllato con placebo ha dimostrato miglioramenti statisticamente significativi nei marker infiammatori del sangue con somministrazione mensile.
I risultati chiave includono la riduzione dei livelli dei marker proinfiammatori CCL2 (p<0.05) e IL-15 (p<0.001), l'aumento della citochina anti-infiammatoria IL-4 (p<0.01), e un miglioramento nel clearance della beta amiloide 42. I pazienti sotto trattamento mensile con LD IL-2 hanno mostrato un miglioramento di 4.93 punti nel punteggio ADAS-Cog rispetto al placebo.
Lo studio ha coinvolto 38 partecipanti di età compresa tra 50 e 86 anni affetti da malattia di Alzheimer. La somministrazione mensile si è dimostrata più efficace rispetto a quella bisettimanale. Il trattamento è stato ben tollerato, senza eventi avversi gravi riportati. Il set di dati completo sarà presentato nel corso del 2025.
Coya Therapeutics (NASDAQ: COYA) reportó resultados positivos de un estudio de Fase 2 sobre IL-2 en baja dosis (LD IL-2) en pacientes con enfermedad de Alzheimer. El ensayo, de 21 semanas, doble ciego y controlado con placebo, demostró mejoras estadísticamente significativas en los marcadores inflamatorios en sangre con dosis mensuales.
Los hallazgos clave incluyen disminuciones en los niveles de los marcadores proinflamatorios CCL2 (p<0.05) y IL-15 (p<0.001), aumento de la citoquina antiinflamatoria IL-4 (p<0.01) y mejora en la eliminación de beta amiloide 42. Los pacientes que recibieron LD IL-2 mensualmente mostraron una mejora de 4.93 puntos en la puntuación ADAS-Cog en comparación con el placebo.
El estudio tuvo 38 participantes de entre 50 y 86 años con enfermedad de Alzheimer. La dosis mensual resultó ser más efectiva que la administración quincenal. El tratamiento fue bien tolerado, sin eventos adversos graves reportados. El conjunto de datos completo se presentará a lo largo de 2025.
Coya Therapeutics (NASDAQ: COYA)는 알츠하이머 환자를 대상으로 한 저용량 IL-2 (LD IL-2)에 대한 2상 연구에서 긍정적인 결과를 보고했습니다. 21주간의 이중 맹검, 위약 대조 시험에서 월별 투여로 통계적으로 유의미한 개선이 염증성 혈액 마커에서 나타났습니다.
주요 발견으로는 염증 유발 마커인 CCL2 (p<0.05)와 IL-15 (p<0.001)의 수준 감소, 항염증 사이토카인 IL-4 (p<0.01)의 증가, 그리고 베타 아밀로이드 42의 제거 개선이 포함됩니다. LD IL-2를 월별로 투여받은 환자들은 위약 대비 ADAS-Cog 점수가 4.93점 향상되었습니다.
이 연구는 50세에서 86세 사이의 알츠하이머 환자 38명을 대상으로 진행되었습니다. 월별 투여가 격주 투여보다 효과적임을 입증했습니다. 치료는 잘 견뎌졌으며 심각한 부작용은 보고되지 않았습니다. 전체 데이터 세트는 2025년 내내 발표될 예정입니다.
Coya Therapeutics (NASDAQ: COYA) a rapporté des résultats positifs d'une étude de phase 2 sur l'IL-2 à faible dose (LD IL-2) chez des patients atteints de la maladie d'Alzheimer. L'essai contrôlé, en double aveugle et avec placebo, d'une durée de 21 semaines a démontré des améliorations statistiquement significatives des marqueurs inflammatoires dans le sang avec une posologie mensuelle.
Les résultats clés incluent la réduction des niveaux de marqueurs pro-inflammatoires CCL2 (p<0.05) et IL-15 (p<0.001), l'augmentation de la cytokine anti-inflammatoire IL-4 (p<0.01), et l'amélioration de l'élimination de la bêta-amyloïde 42. Les patients recevant LD IL-2 mensuellement ont montré une amélioration de 4,93 points dans le score ADAS-Cog par rapport au placebo.
L'étude a impliqué 38 participants âgés de 50 à 86 ans atteints de la maladie d'Alzheimer. La posologie mensuelle s'est révélée plus efficace que l'administration bimensuelle. Le traitement a été bien toléré, sans événements indésirables graves signalés. L'ensemble des données sera présenté tout au long de 2025.
Coya Therapeutics (NASDAQ: COYA) hat positive Ergebnisse aus einer Phase-2-Studie zu niedrig dosiertem IL-2 (LD IL-2) bei Alzheimer-Patienten berichtet. Die 21-wöchige, doppelblinde, placebokontrollierte Studie zeigte statistisch signifikante Verbesserungen bei entzündlichen Blutmarkern mit monatlicher Dosierung.
Zu den wichtigsten Ergebnissen gehören reduzierte Werte der proinflammatorischen Marker CCL2 (p<0.05) und IL-15 (p<0.001), ein Anstieg des antiinflammatorischen Zytokins IL-4 (p<0.01) und eine verbesserte Clearance von Beta-Amyloid 42. Patienten, die monatlich LD IL-2 erhielten, zeigten eine Verbesserung um 4,93 Punkte im ADAS-Cog-Score im Vergleich zur Placebo-Gruppe.
Die Studie umfasste 38 Teilnehmer im Alter von 50 bis 86 Jahren mit Alzheimer. Die monatliche Dosierung erwies sich als effektiver als die zweiwöchentliche Verabreichung. Die Behandlung wurde gut vertragen, und es wurden keine schwerwiegenden Nebenwirkungen gemeldet. Die umfassenden Daten werden im Laufe von 2025 präsentiert.
- Statistically significant reduction in inflammatory markers with monthly dosing
- 4.93-point improvement in ADAS-Cog score vs placebo over 21 weeks
- Increased clearance of amyloid-β in cerebrospinal fluid
- No serious adverse events reported
- Treatment well-tolerated with only mild side effects
- Anti-inflammatory benefits reverted to placebo levels after treatment cessation
- Higher frequency (biweekly) dosing showed smaller impact than monthly dosing
Insights
The latest clinical data from Coya Therapeutics' Phase 2 study of LD IL-2 represents a significant development in the Alzheimer's disease (AD) treatment landscape. The results demonstrate a sophisticated approach to neuroinflammation through Treg modulation, with several noteworthy findings:
The monthly dosing regimen showed superior results compared to biweekly administration, suggesting an optimal therapeutic window for Treg activation. This is evidenced by statistically significant reductions in CCL2 (p<0.05) and IL-15 (p<0.001), alongside increased IL-4 (p<0.01). These biomarker changes are particularly meaningful as they indicate successful modulation of both systemic and central nervous system inflammation.
The 4.93-point improvement in ADAS-Cog scores over 21 weeks is clinically relevant, as a change of 4 points or more is generally considered meaningful in AD trials. The corresponding increase in CSF Aβ42 levels suggests enhanced amyloid clearance, a critical factor in disease modification.
The study's design, involving 38 participants and multiple dosing arms, provides robust preliminary evidence for LD IL-2's potential. The reversion of anti-inflammatory benefits to baseline after treatment cessation validates the biological activity of the therapy while highlighting the need for maintenance treatment.
These results position Coya's approach uniquely in the AD treatment landscape, particularly given the clean safety profile and the potential for combination strategies with other immunomodulatory approaches. The company's plan to explore COYA 301 in combination therapies could address the complex pathology of AD more comprehensively.
The latest clinical results significantly strengthen Coya's market position in the $12.9 billion Alzheimer's disease therapeutics market. The study's robust design and positive outcomes, particularly the meaningful cognitive improvements and clean safety profile, enhance the company's value proposition in several key ways:
First, the demonstrated efficacy with monthly dosing versus biweekly administration has positive implications for commercial viability, potentially reducing treatment burden and costs while maintaining efficacy. This could provide a competitive advantage in market adoption and payer acceptance.
The backing of prestigious institutions (Gates Foundation, Alzheimer's Association, National Institute on Aging) validates the scientific approach and could facilitate future funding or partnerships. The planned publications throughout 2025 will likely increase visibility and could attract potential strategic partners.
The company's strategic positioning with COYA 301 and its combination therapy approach demonstrates commercial foresight, potentially addressing market demands for more comprehensive treatment solutions. The clean safety profile and straightforward subcutaneous administration route could support broad market adoption if approved.
Investigator-initiated data from Houston Methodist Hospital showed LD IL-2 reduced proinflammatory factors, both systemically and within the central nervous system, while demonstrating statistically significant improvement in beta amyloid 42 clearance with stabilization of cognitive decline over a five-month treatment period
Comprehensive data set will be presented and released throughout 2025 and in a peer reviewed publication
Statistically significant reduced levels of proinflammatory markers were observed in patients receiving a five-day treatment of subcutaneous LD IL-2 on a monthly cycle in comparison to a biweekly 5-day administration or placebo. Lower blood levels of the proinflammatory chemokine (C-C motif) ligand 2 (CCL2) (p<0.05) and proinflammatory cytokine IL-15 (p <0.001) were statistically significant, and a statistically significant increase in the anti-inflammatory cytokine IL-4 (p<0.01) in patients receiving monthly cycles of LD IL-2 was observed, compared to patients receiving placebo. At the end of the five-month treatment period when treatment was removed, the anti-inflammatory benefits reverted back to placebo levels. In addition, patients receiving LD IL-2 cycles at the higher biweekly frequency showed a smaller impact on these factors compared to monthly LD IL-2, supporting the potential beneficial effects of monthly LD IL-2.
"We believe the reduction of proinflammatory factors within peripheral blood corresponding with significant improvement in beta amyloid 42 in the cerebrospinal fluid and cognitive stabilization during LD IL-2 therapy underscores the importance of targeting regulatory T cells in Alzheimer’s disease. We believe LD IL-2 offers an immunomodulatory strategy that enhances Treg function for potentially treating Alzheimer’s disease and several other neurodegenerative disorders,” commented Coya CMO Fred Grossman, DO.
The statistically significant improvement in serum inflammatory markers corresponded with previously-reported findings from AD patients receiving monthly LD IL-2 compared to patients receiving biweekly LD IL-2 or placebo. Monthly LD IL-2 showed an increase in Aβ42 levels in cerebrospinal fluid (CSF), suggesting increased clearance of amyloid-β, stable levels of neurofilament light chain (NfL) in CSF, and statistically significant Treg expansion, all demonstrating targeted biological activity. In addition, patients receiving monthly LD IL-2 showed a 4.93-point improvement in the ADAS-Cog score compared to placebo over the 21-week treatment period.
Topline results from this investigator-initiated study were presented in October 2024 at the Clinical Trials on Alzheimer’s Disease Conference (CTAD) in
LD IL-2 was well-tolerated and no serious adverse events (SAEs) or deaths were reported. The most common AEs were mild injection site reactions and a mild increase in eosinophil counts.
LD IL-2 plays a key role in the expansion and immunomodulatory function of Tregs in vivo. LD IL-2 binds to the high affinity interleukin-2 receptor α-chain (IL-2Rα; CD25), which is mainly expressed in Tregs. In contrast, higher doses of IL-2 also bind to the lower affinity IL-2Rβ (CD122), which stimulates proinflammatory T cells and NK cells. The improved biological and clinical effects experienced by patients receiving monthly LD IL-2 administration could be due to selective expansion of Tregs at lower doses, while higher IL-2 doses activate pro-inflammatory pathways.
Coya plans to publish and present the results of this study throughout 2025.
Coya CEO Arun Swaminathan, Ph.D., added, "While monotherapy with LD IL-2 shows targeted improvement in biological activity in patients with AD, as demonstrated in this early Phase 2 academic study, we think that combining our proprietary LD IL-2 (COYA 301) with several other immunomodulatory modalities could deliver additive or even synergistic targeted effects."
Summary of Study Design
The investigator-initiated, randomized, double-blind, placebo-controlled Phase 2 trial evaluated two dosing regimens of subcutaneous LD IL-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 five days of LD IL-2 (106 IU/day) (LD IL-2 q4wks) or placebo every four 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 two weeks (LD IL-2 q2wks) or placebo for the same 21-week duration. All participants were monitored for nine 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.
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 (CTLA4-Ig) and is being developed for subcutaneous administration for the treatment of patients with ALS, FTD, Parkinson’s Diseases (PD), and Alzheimer’s disease. 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 in a small cohort of patients with ALS conducted at the Houston Methodist Research Institute (
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
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.
For more information about Coya, please visit www.coyatherapeutics.com
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Source: Coya Therapeutics, Inc.
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