Abatacept

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 HOUSTON, TX, USA I September 16, 2024 I 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 SOURCE: Coya Therapeutics

HAYWARD, Calif.--( BUSINESS WIRE )--Aqtual, Inc., a precision medicine company with a novel active chromatin cell-free DNA (cfDNA ac ) platform to develop products for chronic diseases and oncology, announced research in Communications Biology , a Nature portfolio journal. The research demonstrates the potential of Aqtual’s proprietary platform that evaluates gene regulation, epigenetics, and transcriptomics by analyzing previously unexplored cfDNA fragments found in blood, opening the door to new clinical applications in almost every major disease area. cfDNA has become pivotal in precision medicine by changing the diagnostic and therapeutic landscape. However, cfDNA platforms have largely been limited to applications in non-invasive prenatal testing, cancer diagnostics and monitoring organ transplantation because they are unable to capture the full range of molecular complexity involved in other disease states. In contrast, this research showed Aqtual’s platform has the potential to expand the clinical utility of cfDNA beyond these areas. By capturing active chromatin fragments (sections of DNA that are associated with regions of the genome where genes are actively being expressed) that reflect gene regulation and molecular changes in real-time, the platform can uncover new biomarkers relevant to a broader range of disease states. “The simple modification of DNA isolation techniques from plasma samples, allowing for enrichment of longer DNA fragments derived from actively transcribed regions, is a major advancement in the cell-free DNA field,” said Clifford Lowell, MD, PhD, Distinguished Professor and Chair at the University of California, San Francisco, Dept. of Laboratory Medicine. “This cell-free DNA sequencing assay can follow the normal circadian rhythm of immune cell gene expression, offering a novel and straightforward method to monitor gene expression profiles in immune and potentially non-immune mediated disease states. It will be exciting to see how this new tool is applied.” Aqtual’s platform provides insights into how genes are controlled and expressed by analyzing DNA fragments from a single blood sample. This approach may enable physicians to diagnose diseases earlier and tailor treatments to individual patients. The ability to monitor gene activity without the need for an invasive procedure opens up a wide range of possibilities for better managing various conditions, including chronic diseases, autoimmune disorders, neurodegenerative diseases, and infectious diseases. "The potential of Aqtual’s platform is vast. For example, globally, 2.6 billion people suffer from some form of chronic disease, with 1 in 3 living with more than one chronic condition,” said Diana Abdueva, PhD, Chief Executive Officer of Aqtual and co-author of the study. “The challenge with managing chronic diseases is that treatment is often trial and error, leading to inefficiencies and poor patient outcomes. In the U.S. alone, 90% of all healthcare spending—over $3.6 trillion—is dedicated to chronic diseases. We believe Aqtual’s platform has the potential to shift this paradigm." Aqtual’s initial focus is developing a blood test to guide therapy management for Rheumatoid Arthritis (RA). RA is a highly debilitating chronic inflammatory disease affecting 1.3 million Americans. 1 With more than 20 FDA-approved drugs across six drug classes, many patients try at least two or three different therapies before finding one that works for them. 2 It is estimated that annual healthcare costs of RA patients in the United States total more than $19B, not including intangible costs like quality of life, premature mortality, and societal costs. 3 Patients living with RA are often on expensive therapeutics for years and often fail to respond to a prescribed treatment; in which case the guidelines recommend switching therapy. "For conditions like RA, there’s a clear opportunity to optimize therapy selection and avoid the wasteful spending associated with ineffective immunotherapy assignments,” continued Dr. Abdueva.“By providing clinicians with a more precise, data-driven approach to treatment, Aqtual’s platform could help ensure patients receive the right therapy sooner, improving both outcomes and cost-efficiency." About Aqtual , Inc. Aqtual, Inc. is a precision medicine company developing products for chronic disease management and oncology utilizing a novel cell-free DNA-based platform. Aqtual’s proprietary platform evaluates protein regulation, epigenetics, and transcriptomics solely using cell-free DNA fragments found in the blood. The platform yields efficient and robust real-time analysis of disease and treatment while overcoming the limitations of previous cell-free DNA methodologies. _____________________________ 1 Xu Y, Wu Q. Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005-2018. J Clin Med. 2021 Jul 26;10(15):3289. doi: 10.3390/jcm10153289. PMID: 34362073; PMCID: PMC8348893. 2 Lauper K, Iudici M, Mongin D, Bergstra SA, Choquette D, Codreanu C, Cordtz R, De Cock D, Dreyer L, Elkayam O, Hauge EM, Huschek D, Hyrich KL, Iannone F, Inanc N, Kearsley-Fleet L, Kristianslund EK, Kvien TK, Leeb BF, Lukina G, Nordström DC, Pavelka K, Pombo-Suarez M, Rotar Z, Santos MJ, Strangfeld A, Verschueren P, Courvoisier DS, Finckh A. Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration. Ann Rheum Dis. 2022 Oct;81(10):1358-1366. doi: 10.1136/annrheumdis-2022-222586. Epub 2022 Jun 15. PMID: 35705376; PMCID: PMC9484385. 3 Birnbaum H, Pike C, Kaufman R, Marynchenko M, Kidolezi Y, Cifaldi M. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin. 2010 Jan;26(1):77-90. doi: 10.1185/03007990903422307. PMID: 19908947.