Cleveland Clinic Lerner Research Institute

Amarna Therapeutics announces formation of Scientific Advisory Board to support advancement of groundbreaking Nimvec™ AM510 gene therapy against Type 1 Diabetes Members: Prof. Dr. Colin Dayan, Prof. Dr. Desmond Schatz, Prof. Dr. Didac Mauricio, Dr. Luiza Caramori, Dr. Kei Kishimoto, Prof. Dr. Roberto Mallone, Dr. Sylvaine You. Leiden, The Netherlands, 17 June 2024 – Amarna Therapeutics, (“Amarna” or “the Company”) a privately-held biotechnology company focused on developing transformative gene therapies for a range of rare and prevalent genetic diseases, including Type 1 Diabetes Mellitus (T1DM), is pleased to announce the formation of its new Scientific Advisory Board (SAB).The newly established SAB consists of seven distinguished international scientific opinion leaders. These experts bring extensive experience and knowledge in the fields of pre-clinical and clinical development, gene therapy, immunology, endocrinology, and regulatory affairs. The SAB will leverage its extensive expertise to ensure that Amarna’s groundbreaking Nimvec™ AM510 program meets the highest scientific and regulatory standards. This initiative underscores the company's commitment to pioneering treatments for T1DM and enhancing patient outcomes. The SAB's insights will be pivotal in navigating the complex landscape of clinical trials and regulatory approvals, ultimately accelerating the path to market for this groundbreaking therapy. “The formation of this Scientific Advisory Board marks a major development step for Amarna as we continue our evolution in becoming a clinical stage gene therapy development company,” said Henk Streefkerk, CEO of Amarna. “We are proud and excited to bring together leading clinicians and scientists from across the world who are dedicated to, and have decades of experience in, the clinical development of novel therapeutics for genetic diseases. We believe their collective expertise will be instrumental in guiding Amarna advancing its lead drug candidate, Nimvec™ AM510, as we work to optimize its potential to transform the treatment of Type 1 Diabetes Mellitus and a range of other prevalent debilitating genetic disorders.” The members of the Scientific Advisory Board (SAB) are as follows: Colin Dayan, MA MBBS, FRCP, PhD, is Professor of Clinical Diabetes and Metabolism at Cardiff University School of Medicine, in Cardiff (UK), Senior Clinical Researcher at the University of Oxford and Director at the Cardiff Joint Research Office. His focus lies mainly on translational research in immunopathology of Type 1 Diabetes Mellitus, clinical trials on peptide immunotherapy and nanoparticles in T1DM. Desmond Schatz, MD, PhD, is Professor of Pediatrics, Medical Director of the Diabetes Institute, and Medical Director of the Clinical Research Center, at the University of Florida, and served as President of Science and Medicine of the American Diabetes Association (2016). Dr. Schatz has been involved in Type 1 diabetes research since the mid 1980’s and has published over 400 manuscripts, the majority related to the prediction, natural history, genetics, immunopathogenesis and prevention of the disease, as well as the management of children and adolescents with Type 1 diabetes. Didac Mauricio, MD, PhD, is Director of the Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau in Barcelona, and Professor with the Faculty of Medicine, University of Vic & Central University of Catalonia (UVic/UCC). He is leading the Diabetes Research Group at his current institution and has recently been appointed Scientific Director of the CIBER of Diabetes and Associated Metabolic diseases (CIBERDEM), Instituto de Salud Carlos III (Ministry of Science and Innovation), in Spain. Luiza Caramori, MD, MSc, PhD, is a Staff Physician at the Institute of Endocrinology and Metabolism at Cleveland Clinic Foundation and at the Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio (USA) and an Adjunct Associate Professor at the University of Minnesota, Minneapolis, MN (USA). Dr. Caramori’s is a physician-scientist with 25+ years research experience, whose main research interests include studies on the relationships between kidney structure and function in type 1 diabetes, early molecular and structural predictors of diabetic kidney disease (DKD) in patients with type 1 diabetes, and clinical trials studying repurposed and new drugs for the prevention and treatment of DKD both in patients with type 1 and type 2 diabetes. Kei Kishimoto, PhD, is a highly accomplished immunologist and drug developer with over 30 years of experience in biopharma. He was most recently Chief Scientific Officer of Selecta Biosciences, where he led development of an immune tolerance technology that was successfully validated in Phase 3 clinical trials. Prior to joining Selecta, he was Vice President of Research at Momenta Pharmaceuticals and Senior Director Inflammation at Millennium Pharmaceuticals. His expertise is focused on immunology, immune tolerance, autoimmune diseases, vaccines, immunogenicity and gene therapy. Kei Roberto Mallone, MD, PhD, is Professor and Hospital Physician in Clinical Immunology and Diabetology at Paris Cité University - Cochin Hospital and Research Director at INSERM U1016 Cochin Institute in Paris, France and at the Indiana Biosciences Research Institute (IBRI) in Indianapolis (USA). His research spans from preclinical studies with human samples and mouse models to clinical trials. It focuses on autoimmune T cells and beta-cell vulnerability and the understanding of type 1 diabetes mechanisms to develop T-cell-based biomarkers and therapeutics aimed at blunting T-cell aggressiveness and enhancing beta-cell resilience. Sylvaine You, MD, PhD, is a distinguished researcher specializing in the immune mechanisms driving type 1 diabetes (T1DM) and the development of therapeutic strategies. She is Research Director at Cochin Institute (INSERM) in Paris, France, focuses on T-cell Tolerance, Biomarkers and Therapies in type 1 Diabetes. Additionally, she co-leads a research team at the Indiana Biosciences Research Institute (IBRI), exploring the mechanisms that fail to keep autoreactive T lymphocytes inoffensive and make the beta cells more visible and vulnerable to an autoimmune attack. === E N D S === About Type 1 Diabetes MellitusType 1 Diabetes is a debilitating disease occurring in millions of patients globally, with rising incidences each year, where despite advancements in therapy the life expectancy remains lower than the general population. Diabetes is an autoimmune disease where self-reactive T lymphocytes selectively attack and destroy insulin-producing β cells lodged within the pancreas, leaving the patient unable to maintain glucose homeostasis. Proinsulin (PI) is the primary self-antigen involved in the autoimmune β cell destruction. To date, Type 1 Diabetes cannot be cured, and the glucose homeostasis can be more or less maintained in patients by daily insulin injections. Although Diabetes is seen as a manageable disease nowadays, secondary complications of the current therapy are considerable and lead to significant morbidity and mortality. Using Nimvec™ AM510 we intend to restore the immune tolerance to proinsulin and potentially cure the patients. About Nimvec™ AM510The development of AM510 is based on our proprietary NimvecTM platform, which has demonstrated exceptional promise in preclinical studies. Unlike other gene therapies that induce a strong immune response, limiting the possibility for repeat dosing and efficacy, NimvecTM does not trigger such responses. Instead, it moderates the immune system to induce tolerance, making it an ideal vehicle for our therapeutic approach. Our preclinical data with Nimvec™ AM510 showcases its protective effects in delaying the onset of hyperglycemia and preventing the development of T1DM in relevant animal models. About AmarnaAmarna Therapeutics has developed a groundbreaking non-immunogenic viral platform NimvecTM to deliver any transgene of choice into humans. This platform shows exceptional promise in preclinical studies for delivering treatments, potential cures, and disease prevention globally. Amarna is advancing a pipeline of transformative gene therapies for a range of rare and prevalent diseases, including monogenetic indications, autoimmune diseases and chronic inflammation. The lead program Nimvec™ AM510 is being developed for the treatment of patients with Type 1 Diabetes Mellitus. Follow up programs include Multiple Sclerosis, Age-related Macular Degeneration, and Hemophilia. More information on www.amarnatherapeutics.com Follow us on LinkedIn https://www.linkedin.com/company/amarna-therapeutics-b.v. For further inquiries please contact: Amarna TherapeuticsHenk Streefkerk, CEOE-mail: info@amarnatherapeutics.com LifeSpring Life Sciences Communication, AmsterdamLéon MelensTel: +31 6 538 16 427E-mail: lmelens@lifespring.nl

MONDAY, June 17, 2024 -- Xylitol is associated with incident major adverse cardiovascular event (MACE) risk, according to a study published online June 6 in the European Heart Journal . Marco Witkowski, M.D., from the Lerner Research Institute at the Cleveland Clinic, and colleagues performed untargeted metabolomics studies on overnight fasting plasma samples in a discovery cohort of 1,157 sequential stable patients undergoing elective diagnostic cardiac evaluations. Subsequent isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent validation cohort comprising 2,149 participants. The effect of xylitol on platelet responsiveness and thrombus formation in vivo was examined in complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies. Finally, the effects of xylitol consumption were examined on platelet function in 10 healthy volunteers. The researchers found that circulating levels of a polyol tentatively assigned as xylitol were associated with incident MACE risk in the initial untargeted metabolomics study (discovery cohort). The association of xylitol with incident MACE risk was confirmed in stable isotope dilution LC-MS/MS analyses (third versus first tertile adjusted hazard ratio, 1.57). Xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma were seen in complementary mechanistic studies. Xylitol-sweetened drinks markedly raised plasma levels in interventional studies, and enhanced multiple functional measures of platelet responsiveness in all individuals. "Our studies suggest that xylitol will likely confer heightened thrombosis potential in the same vulnerable patients that it is marketed towards and intended to protect," the authors write. Several authors disclosed ties to the biopharmaceutical industry; several authors are named coinventors on pending and issued patents relating to cardiovascular diagnostics and therapeutics.

Amarna Therapeutics announces formation of Scientific Advisory Board to support advancement of groundbreaking Nimvec™ AM510 gene therapy against Type 1 Diabetes Members: Prof. Dr. Colin Dayan, Prof. Dr. Desmond Schatz, Prof. Dr. Didac Mauricio, Dr. Luiza Caramori, Dr. Kei Kishimoto, Prof. Dr. Roberto Mallone, Dr. Sylvaine You. Leiden, The Netherlands, 17 June 2024 – Amarna Therapeutics, (“Amarna” or “the Company”) a privately-held biotechnology company focused on developing transformative gene therapies for a range of rare and prevalent genetic diseases, including Type 1 Diabetes Mellitus (T1DM), is pleased to announce the formation of its new Scientific Advisory Board (SAB). The newly established SAB consists of seven distinguished international scientific opinion leaders. These experts bring extensive experience and knowledge in the fields of pre-clinical and clinical development, gene therapy, immunology, endocrinology, and regulatory affairs. The SAB will leverage its extensive expertise to ensure that Amarna’s groundbreaking Nimvec™ AM510 program meets the highest scientific and regulatory standards. This initiative underscores the company's commitment to pioneering treatments for T1DM and enhancing patient outcomes. The SAB's insights will be pivotal in navigating the complex landscape of clinical trials and regulatory approvals, ultimately accelerating the path to market for this groundbreaking therapy. “The formation of this Scientific Advisory Board marks a major development step for Amarna as we continue our evolution in becoming a clinical stage gene therapy development company,” said Henk Streefkerk, CEO of Amarna. “We are proud and excited to bring together leading clinicians and scientists from across the world who are dedicated to, and have decades of experience in, the clinical development of novel therapeutics for genetic diseases. We believe their collective expertise will be instrumental in guiding Amarna advancing its lead drug candidate, Nimvec™ AM510, as we work to optimize its potential to transform the treatment of Type 1 Diabetes Mellitus and a range of other prevalent debilitating genetic disorders.” The members of the Scientific Advisory Board (SAB) are as follows: Colin Dayan, MA MBBS, FRCP, PhD, is Professor of Clinical Diabetes and Metabolism at Cardiff University School of Medicine, in Cardiff (UK), Senior Clinical Researcher at the University of Oxford and Director at the Cardiff Joint Research Office. His focus lies mainly on translational research in immunopathology of Type 1 Diabetes Mellitus, clinical trials on peptide immunotherapy and nanoparticles in T1DM. Desmond Schatz, MD, PhD, is Professor of Pediatrics, Medical Director of the Diabetes Institute, and Medical Director of the Clinical Research Center, at the University of Florida, and served as President of Science and Medicine of the American Diabetes Association (2016). Dr. Schatz has been involved in Type 1 diabetes research since the mid 1980’s and has published over 400 manuscripts, the majority related to the prediction, natural history, genetics, immunopathogenesis and prevention of the disease, as well as the management of children and adolescents with Type 1 diabetes. Didac Mauricio, MD, PhD, is Director of the Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau in Barcelona, and Professor with the Faculty of Medicine, University of Vic & Central University of Catalonia (UVic/UCC). He is leading the Diabetes Research Group at his current institution and has recently been appointed Scientific Director of the CIBER of Diabetes and Associated Metabolic diseases (CIBERDEM), Instituto de Salud Carlos III (Ministry of Science and Innovation), in Spain. Luiza Caramori, MD, MSc, PhD, is a Staff Physician at the Institute of Endocrinology and Metabolism at Cleveland Clinic Foundation and at the Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio (USA) and an Adjunct Associate Professor at the University of Minnesota, Minneapolis, MN (USA). Dr. Caramori’s is a physician-scientist with 25+ years research experience, whose main research interests include studies on the relationships between kidney structure and function in type 1 diabetes, early molecular and structural predictors of diabetic kidney disease (DKD) in patients with type 1 diabetes, and clinical trials studying repurposed and new drugs for the prevention and treatment of DKD both in patients with type 1 and type 2 diabetes. Kei Kishimoto, PhD, is a highly accomplished immunologist and drug developer with over 30 years of experience in biopharma. He was most recently Chief Scientific Officer of Selecta Biosciences, where he led development of an immune tolerance technology that was successfully validated in Phase 3 clinical trials. Prior to joining Selecta, he was Vice President of Research at Momenta Pharmaceuticals and Senior Director Inflammation at Millennium Pharmaceuticals. His expertise is focused on immunology, immune tolerance, autoimmune diseases, vaccines, immunogenicity and gene therapy. KeiRoberto Mallone, MD, PhD, is Professor and Hospital Physician in Clinical Immunology and Diabetology at Paris Cité University - Cochin Hospital and Research Director at INSERM U1016 Cochin Institute in Paris, France and at the Indiana Biosciences Research Institute (IBRI) in Indianapolis (USA). His research spans from preclinical studies with human samples and mouse models to clinical trials. It focuses on autoimmune T cells and beta-cell vulnerability and the understanding of type 1 diabetes mechanisms to develop T-cell-based biomarkers and therapeutics aimed at blunting T-cell aggressiveness and enhancing beta-cell resilience. Sylvaine You, MD, PhD, is a distinguished researcher specializing in the immune mechanisms driving type 1 diabetes (T1DM) and the development of therapeutic strategies. She is Research Director at Cochin Institute (INSERM) in Paris, France, focuses on T-cell Tolerance, Biomarkers and Therapies in type 1 Diabetes. Additionally, she co-leads a research team at the Indiana Biosciences Research Institute (IBRI), exploring the mechanisms that fail to keep autoreactive T lymphocytes inoffensive and make the beta cells more visible and vulnerable to an autoimmune attack. === E N D S === About Type 1 Diabetes Mellitus Type 1 Diabetes is a debilitating disease occurring in millions of patients globally, with rising incidences each year, where despite advancements in therapy the life expectancy remains lower than the general population. Diabetes is an autoimmune disease where self-reactive T lymphocytes selectively attack and destroy insulin-producing β cells lodged within the pancreas, leaving the patient unable to maintain glucose homeostasis. Proinsulin (PI) is the primary self-antigen involved in the autoimmune β cell destruction. To date, Type 1 Diabetes cannot be cured, and the glucose homeostasis can be more or less maintained in patients by daily insulin injections. Although Diabetes is seen as a manageable disease nowadays, secondary complications of the current therapy are considerable and lead to significant morbidity and mortality. Using Nimvec™ AM510 we intend to restore the immune tolerance to proinsulin and potentially cure the patients. About Nimvec™ AM510 The development of AM510 is based on our proprietary NimvecTM platform, which has demonstrated exceptional promise in preclinical studies. Unlike other gene therapies that induce a strong immune response, limiting the possibility for repeat dosing and efficacy, NimvecTM does not trigger such responses. Instead, it moderates the immune system to induce tolerance, making it an ideal vehicle for our therapeutic approach. Our preclinical data with Nimvec™ AM510 showcases its protective effects in delaying the onset of hyperglycemia and preventing the development of T1DM in relevant animal models. About Amarna Amarna Therapeutics has developed a groundbreaking non-immunogenic viral platform NimvecTM to deliver any transgene of choice into humans. This platform shows exceptional promise in preclinical studies for delivering treatments, potential cures, and disease prevention globally. Amarna is advancing a pipeline of transformative gene therapies for a range of rare and prevalent diseases, including monogenetic indications, autoimmune diseases and chronic inflammation. The lead program Nimvec™ AM510 is being developed for the treatment of patients with Type 1 Diabetes Mellitus. Follow up programs include Multiple Sclerosis, Age-related Macular Degeneration, and Hemophilia. More information on Follow us on LinkedIn . For further inquiries please contact: Amarna Therapeutics Henk Streefkerk, CEO E-mail: info@amarnatherapeutics.com LifeSpring Life Sciences Communication, Amsterdam Léon Melens Tel: +31 6 538 16 427 E-mail: lmelens@lifespring.nl