LOX-1

AUSTIN, Texas, April 14, 2023 /PRNewswire/ -- The main results of the Magnetic Resonance Imaging Evaluation of Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (MAGMA) trial, a National Heart, Lung, and Blood Institute (NHLBI) sponsored trial were presented. Although the results of the trial are not final, they offer valuable information for patients using the generic drug Spironolactone. This drug therapy activates white cells and reduces tissue damage as well as reduces proteins that would normally be considered inflammatory. The results from this study will be presented at the National Kidney Foundation's (NKF) NKF Spring Clinical Meetings during the "late-breaking presentations" at the largest multidisciplinary gathering of kidney care professionals in North America from April 11-15 in Austin, Texas. My message to patients is to consider using Spironolactone as their generic drug choice if they can. QUOTE FROM RESEARCHER "My message to patients is to consider using Spironolactone as their generic drug choice if they can for appropriate indications. We want to consider using this drug in high-risk patients with diabetes and atherosclerosis, because the benefit of the drug might extend not only to preventing heart failure and kidney disease progression but potentially other benefits," explained Sanjay Rajagopalan, MD, FACC, FAHA, Chief of the Division of Cardiovascular Medicine and Chief Academic and Scientific Officer of UH Harrington Heart & Vascular Institute; Herman K. Hellerstein, MD, Chair in Cardiovascular Research and a professor at the Case Western Reserve University School of Medicine. "Having a drug that works on these systems in a connective manner is a big benefit to a patient, and this drug happens to be one of those." Highlights of the interim results include: Results: Seventy-nine patients were randomized at 4 sites in US and Canada to Spironolactone (n=37) vs placebo (n=42) for 12 months, after a 2-week single-blind placebo lead-in period and 4-week dose escalation phase. Mean age was 64±8 years; HbA1c 7.3±1.3%; eGFR 44 ml/min/1.73m2; baseline systolic BP 132 ±19 mmHg. The results demonstrated a marked reduction in thoracic plaque volume (Percent change in wall volume) response to Spironolactone at the end of 12 months compared to placebo. These changes were accompanied by changes in left ventricular mass and fibrosis. Spironolactone treatment did not change clinic systolic blood pressure but did cause a statistically significant change in 24-hour mean systolic and diastolic blood pressures compared to baseline and versus placebo respectively. Spironolactone also reduced LV wall mass and a measure of LV fibrosis (native T1 values). Plasma proteomic analysis revealed significant downregulation of a number of pathways involved in immune activation/inflammation, leukocyte activation, proliferation and pathways involved in cytokine stimulation. The top 2 molecules downregulated were DDR2, and oxidized LDL receptor-1 (LOX-1) involved in collagen synthesis and inflammation respectively. Additional top downregulated proteins included known Aldosterone targets such as Sodium/potassium-transporting ATPase subunit beta-3 and Adenylyl cyclase-associated protein 1. Data are mean ± SD. Change was defined as the value at 12 months minus the value at baseline. †p < 0.05; †††p < 0.001 Thousands of kidney care professionals will attend the Spring Clinical Meetings in-person and virtually. Hundreds of the latest studies and kidney care advances will be unveiled. NKF Spring Clinical Meetings For the past 31 years, nephrology healthcare professionals from across the country have come to NKF's Spring Clinical Meetings to learn about the newest developments related to all aspects of nephrology practice; network with colleagues; and present their research findings. The NKF Spring Clinical Meetings are designed for meaningful change in the multidisciplinary healthcare teams' skills, performance, and patient health outcomes. It is the only conference of its kind that focuses on translating science into practice for the entire healthcare team. About Kidney Disease In the United States, more than 37 million adults are estimated to have kidney disease, also known as chronic kidney disease (CKD)—and approximately 90 percent don't know they have it. About 1 in 3 adults in the U.S. are at risk for kidney disease. Risk factors for kidney disease include: diabetes, high blood pressure, heart disease, obesity, and family history. People of Black or African American, Hispanic or Latino, American Indian or Alaska Native, Asian American, or Native Hawaiian or Other Pacific Islander descent are at increased risk for developing the disease. Black or African American people are about four times as likely as White people to have kidney failure. Hispanics experience kidney failure at about double the rate of White people. NKF Professional Membership Healthcare professionals can join NKF to receive access to tools and resources for both patients and professionals, discounts on professional education, and access to a network of thousands of individuals who treat patients with kidney disease. Media Contacts:

Phase 2a publication entitled “Combined Regulatory T-Lymphocyte and IL-2 Treatment is Safe, Tolerable, and Biologically Active for One Year in Persons with Amyotrophic Lateral Sclerosis” has been published in peer-reviewed journal Neurology, Neuroimmunology & Neuroinflammation COYA 101 was well tolerated and increased Treg suppressive function The majority (6 out of 8) of patients either slowed or stopped progression (mean change of -2.7 points on ALSFRS-R score) during the open label extension over a 24-week period while 2 out of 8 patients did not benefit from treatment Assessment of biomarkers of inflammation and oxidative stress over the course of the study correlated with ALS disease severity and may serve to prospectively evaluate and/or monitor treatment response HOUSTON, Sept. 01, 2022 (GLOBE NEWSWIRE) -- Coya Therapeutics, Inc. (“Coya”), a clinical-stage biotechnology company developing multiple approaches that aim to enhance regulatory T cells (Tregs) function, including allogeneic Treg-derived exosome therapeutics and novel biologics, today announced the publication of the Phase 2a clinical trial data for its first-in-class Treg cell therapy product candidate, COYA 101. Coya has an exclusive worldwide license from Houston Methodist Hospital to develop, manufacture, and commercialize COYA 101. The article entitled “Combined Regulatory T-Lymphocyte and IL-2 Treatment is Safe, Tolerable, and Biologically Active for One Year in Persons with Amyotrophic Lateral Sclerosis” has been published online in the peer-reviewed journal Neurology, Neuroimmunology, & Neuroinflammation. Subjects enrolled in the Phase 2a trial were initially randomized into a double-blind portion to receive active Treg cells or matching placebo every four weeks over 24 weeks. After completion of the 24-week double-blind (DB) portion, subjects entered an open-label extension (OLE) during which all patients received active Treg cells every four weeks for additional 24 weeks. The DB portion of the trial was curtailed due to COVID-19-related restrictions, and the limited number of patients enrolled made statistical analysis not feasible. However, the eight patients included in the OLE completed the 24-week study, and 75% (n=6) of them exhibited slow to no progression as measured by the ALSFRS-R (mean decline of -2.7 points). A sub-analysis of these six patients showed that four of them (50% of the intention-to-treat [ITT] patient population, n=8) exhibited no decline over the 24-week treatment period. The two remaining patients in the OLE did not experience a treatment benefit. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) is a validated rating instrument that gauges the progression of disability in patients with amyotrophic lateral sclerosis (ALS) on a 48-point scale. In addition to the benefit experienced by the majority of patients in clinical function, Treg suppressive function was higher following infusions, compared to baseline values at screening. An unbiased proteomics assay of the OLE specimens documented that the two rapidly progressing patients had markedly higher levels of biomarkers of inflammation (IL-17F and IL-17C) and oxidative stress (OLR1 and ox-LDL) compared to the other six patients who exhibited amelioration or halting of disease progression, representing important findings that may provide new tools to identify the most suitable ALS patients for the next well-powered and well controlled trial. Overall, treatment with COYA 101 was well tolerated. No deaths were reported and no patient receiving Treg infusions were discontinued from the study. Howard Berman, Ph.D., Chief Executive Officer of Coya, stated, “We believe this Phase 2a study, with the limitations of a small sample size, supports that COYA 101 was well tolerated and biologically active in ALS patients and may slow or halt disease progression in the right patient population. We believe the findings that high levels of inflammation and oxidative stress may limit the effectiveness of Tregs, resulting in shorter cell half-lives and impacting their downstream suppressive anti-inflammatory effects, may help to better enhance the signal by prospectively identifying the patients with the higher likelihood to respond,” concluded Dr. Berman. “We are encouraged by the results from this study, which are consistent with the positive outcomes of the previous Phase 1 trial in ALS patients. We believe these results are relevant, as they provide information we need to design our next double-blind controlled study to assess the efficacy and safety of COYA 101,” added Adrian Hepner, M.D, Ph.D., President and Chief Medical Officer of Coya. Stanley H. Appel, M.D., the Chair of the Scientific Advisory Board of Coya, stated, “Although the double-blind portion of the Phase 2a study was compromised by COVID-19, we believe the Open Label Extension supports the findings of our Phase 1 study that COYA 101 infusions are well tolerated, may enhance suppressive functions and may have the potential to slow disease progression.” The online publication can be accessed at About Coya Therapeutics, Inc. Headquartered in Houston, TX, Coya Therapeutics, Inc. (Coya) is a clinical-stage biotechnology company developing approaches utilizing Treg modifying therapeutics to target systemic and neuro inflammation. Coya has pioneered the ability to produce Tregs with a highly suppressive phenotype (“Super Tregs”) from a patient’s own dysfunctional Tregs. "Super Tregs” confer their properties through reproducible upregulated proteins in the expanded/post cryopreserved condition that allow for an off-the-shelf like approach for serial infusion. Coya is also developing exosome therapies derived from “Super Tregs” for allogeneic applications, as well as a biologic that works to upregulate Treg function in vivo. Coya is focused on the advancement of disease modifying approaches to address the significant unmet medical needs of patients with Amyotrophic Lateral Sclerosis (ALS), Frontal Temporal Dementia (FTD), Scleroderma, and Hepatic Inflammation and Fibrosis. For more information, please visit . Contacts Investor Contact David Snyder david@coyatherapeutics.com Media Contact Jessica Starman media@coyatherapeutics.com

A key molecule for cancer metastasis has been identified as a molecule already known for its involvement in cardiovascular disease, suggesting a possible treatment approach for both diseases simultaneously. A key molecule for cancer metastasis has been identified as a molecule already known for its involvement in cardiovascular disease, suggesting a possible treatment approach for both diseases simultaneously. Cancer is the uncontrolled growth of body cells leading to the formation of tumors, triggered by the accumulation of mutations in a cell's genome. In order to become malignant, metastasizing cancer, tumor cells go through a series of transformations involving interactions between the body's immune system and the tumor. However, many mechanistic details in this process are still unclear, making the prevention and treatment of cancer notoriously difficult. However, there is growing evidence that in tumor progression to metastasis, inflammation of blood vessel-lining "endothelial" cells is a key process. Concerned with the molecular mechanism behind this process in cancer malignancy, a team of researchers led by Professor Kyoko Hida at Hokkaido University have discovered that, in malignant tumors, endothelial cells accumulate a lipid delivery molecule called "low-density lipoprotein" (LDL) and attract immune cells called "neutrophils." Neutrophils are immune suppressor cells which are known to contribute to tumor progression. The discovery was published in the International Journal of Cancer. Previous work by the team had revealed that blood vessels in malignant tumors expressed a high level of proteoglycans, and it is known that cancerous tissue is inflamed. These features are similar to what is seen in atherosclerosis, and the team wished to investigate if the similarities went deeper. The research team showed that metastasizing tumors, in contrast to non-metastasizing ones, accumulate proteoglycan molecules; these, in turn, attach to and accumulate LDL to the walls of blood vessels. The bound LDL becomes oxidized. There are also high levels of its receptor, called "LOX-1," in the blood vessel-lining endothelial cells of metastasizing tumors. This, they found, causes these cells to produce inflammation signals that attract neutrophils. They then proved that in mice, the suppression of LOX-1 can significantly reduce tumor malignancy, and also that LOX-1 overexpression caused an increase in signaling molecules attracting neutrophils. As the team hypothesized, this sequence of interactions observed in malignant tumors is not novel: it occurs in atherosclerosis, the hardening of blood vessels. "Atherosclerosis and cancer appear to be completely different diseases, but they share several common pathophysiological features in the blood vessels," says Kyoko Hida. Even though some questions remain open, especially on the mechanism of how neutrophils contribute to cancer malignancy, this study is the first to explicitly prove the mechanistic commonalities between cardiovascular disease and cancer progression and trace the mechanism involving LDL accumulation and LOX-1 expression in in-vivo tumor tissue. "Our present study focused on the importance of LOX-1 in endothelial cells as a common factor between cancer and atherosclerosis," Hida explains. "The presence of neutrophils in tumors is a telltale sign of tumor progression." The study also points to a promising approach for treating and preventing malignant cancer -- and cardiovascular disease -- by targeting neutrophil recruitment to endothelial cells. Hida concludes: "The number of patients with cancer who die not of cancer, but of cardiovascular events, is increasing. Targeting the LOX-1/oxidized LDL axis might be a promising strategy for the treatment of the two diseases concomitantly."