Latvijas Organiskas Sintezes Instituts

Preclinical data shows precision modulation of beta-2 and beta-3 signaling boosts metabolism and enhances body recomposition STOCKHOLM, Sweden, May 24, 2024 (GLOBE NEWSWIRE) -- Atrogi, a pioneering clinical-stage biotech company advancing treatments for metabolic disorders, announces a publication in the Journal of Molecular Metabolism (1). The research paper validates the mechanism of action of the company’s first-in-class, small molecule, ATR-127, in combating obesity and metabolic complications. Unlike existing anti-obesity therapies that compromise lean muscle mass, ATR-127 induces significant weight loss while preserving crucial lean body mass. ATR-127 binds to both the beta-2 and beta-3 adrenergic receptors in a unique manner, allowing for precise modulation of downstream signaling cascades. Unlike conventional approaches, ATR-127's innovative binding mechanism enables selective activation of specific signaling pathways. This unlocks the full therapeutic potential of beta-2 and beta-3 receptor agonism, maximizing beneficial effects on metabolism and body composition while mitigating the cardiovascular side effects commonly associated with indiscriminate receptor activation. Atrogi’s CEO, Alexandra Ekman Ryding, said, “This publication highlights strong pre-clinical data relating to ATR-127 and validates our approach for the development of a novel modality for the treatment of obesity. We are now advancing our next generation small molecules for the treatment of obesity to IND preparatory studies in H1 next year and expect to enter the clinic in 2026.” Atrogi´s founder and CSO, Tore Bengtsson, a Professor of Physiology at Stockholm University, said, “There is a high demand for novel treatments of obesity without the current debilitating side effects and muscle loss. We believe our pioneering dual receptor beta-agonist approach has the potential to transform the obesity treatment landscape. Our vision is for a more holistic treatment for diabesity and steatohepatitis that not only treats the underlying cause of disease but also supports overall health and quality of life.” The study found that ATR-127 enhances energy expenditure and promotes beneficial metabolic changes by inducing skeletal muscle glucose uptake and the concomitant activation of brown and beige adipose tissue. This results in healthy weight loss - decreasing fat mass but preserving muscle, whilst reducing hepatic inflammation and lipid content. ATR-127’s ability to deliver precise signaling modulation prevents excessive cAMP production thereby lowering cardiac force production and mitigating risks of cardiovascular side effects. This study was a collaborative international effort involving Atrogi AB, and institutions in Europe and Australia, including Stockholm University, Monash University, University of Nottingham, Karolinska Institute, Maastricht University Medical Center, Latvian Institute of Organic Synthesis, Excellerate Bioscience, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Tübingen University, University of Copenhagen, University of Queensland, and Queensland University of Technology. Atrogi’s unique platform enables the synthesis of compounds capable of modulating signaling downstream of adrenergic receptors in novel ways. By measuring the specific activation of numerous downstream signaling events, Atrogi has created a proprietary library of compounds that engage discrete signaling pathways, each tailored to enhance beneficial effects while mitigating potential side effects in different therapeutic areas. Atrogi's iterative approach to drug development allows for the generation of compounds with optimized signaling profiles and improved efficacy. References (1) Paper: “The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis” Notes to Editors About Atrogi AB Atrogi is a clinical-stage biotech company developing first-in-class, insulin-independent treatments for type 2 diabetes (T2D) and related metabolic disorders, including obesity and muscle-wasting disorders. Atrogi’s lead compound, ATR-258 for T2D, completed a Phase 1a/b clinical trial in March 2024, with Phase II trials planned by the end of 2024. Atrogi also has compounds in pre-clinical development for the treatment of obesity and muscle wasting disorders. ATR-258 binds to the beta-2 adrenoreceptor, initiating a process that mediates the transportation of glucose into skeletal muscle, lowering blood glucose levels and positively affecting several organs affected by T2D. The proprietary small-molecule compound activates the receptor in a novel manner, causing selective modulation and a distinct signaling profile. Atrogi’s platform extends beyond the adrenergic receptor system, offering the potential for application to other GPCRs. By leveraging the signaling complexity of GPCRs, Atrogi aims to develop tailored compounds that engage specific pathways relevant to different clinical conditions, paving the way for safer, more effective therapies. The company has raised over EUR 24 m in total since inception from investors, including Flerie Invest, Korea Investment Partners (KIP) and private investors. This includes a SEK 90 million (approx. EUR 7.6 m) rights issue. The company has also been awarded non-dilutive grants of over EUR 1.5 million from international organizations such as Eurostars, as well as grants from SweLife in recognition of the company’s unique discovery of receptor signaling. The company is based in Solna, near Stockholm, Sweden. Follow the company on LinkedIn and visit its website. Media Contacts Atrogi Alexandra Ekman Ryding, CEO alexandra@atrogi.com Scius Communications (for Atrogi) Katja Stout katja@sciuscommunications.com Tel: +44 7789 435990 Daniel Gooch Tel: +44 7747 875479 daniel@sciuscommunications.com

Secarna has joined forces with the Latvian Institute of Organic Synthesis, the leading drug discovery and development center in the Baltics, the Institute of Bioinformatics (Medical University of Innsbruck) and Innoplexus AG, the leading Artificial Intelligence (AI) platform for drug discovery to identify biomarkers correlating with tumor-induced resistance pathways The consortium aims to further understand the tumor microenvironment and explore the role of ASOs as a new tool for targeted immunotherapy MUNICH, GERMANY and MARTINSRIED, GERMANY / ACCESSWIRE / October 25, 2021 / Secarna Pharmaceuticals GmbH & Co. KG ("Secarna"), a biopharmaceutical company focusing on the discovery and development of next generation antisense oligonucleotide (ASO) therapies to address challenging or previously undruggable targets via its LNAplusTM platform, has joined forces with the Latvian Institute of Organic Synthesis, the leading drug discovery and development center in the Baltics, the Institute of Bioinformatics (Medical University of Innsbruck), with renowned experts in next generation sequencing (Dr. Anne-Margrethe Krogsdam Christensen) as well as computational cancer immunology and data analysis (Priv.-Doz. Dr. Hubert Hackl) to investigate the tumor microenvironment, and Innoplexus AG, the leading Artificial Intelligence (AI) platform for drug discovery. The newly founded consortium aims to improve the efficacy of personalized treatment of cancer patients by exploring the role of ASOs as a new tool for targeted immunotherapy, based on a better understanding of tumor microenvironment functions and their impact on the disease course. Tumors do not exclusively exist in the body as isolated, heterogenous cancer cells, but are also formed by a variety of resident and infiltrating host cells, secreted factors, and extracellular matrix proteins, collectively known as the tumor microenvironment (TME). Within the TME, immune cells are modified to protect the cancer cells against the body's own immune system and enable them to grow. To target these aberrant immune cells and ultimately enhance immune responses, different antibody-based immunotherapies have been developed. However, these treatments are only efficient in a small subset of patients and, in some cases, can show severe side effects. Currently, the underlying cause for this is unknown and so far no biomarkers have been identified that can predict an immune response. Therefore, the development of new approaches to further understand the TME and identify novel biomarkers is of essence to improve patient care. Working together to identify biomarkers correlating with tumor-induced resistance pathways Secarna has developed antisense oligonucleotides (ASOs) targeting core immune metabolic pathways which are generally aberrantly up-regulated within the TME, allowing the cancer to evade the immune response: The adenosine axis (CD39 and CD73) and the kynurenine axis (TDO1- IDO). In this context, the up-regulation of these pathways can be observed through the increase of certain metabolites, such as adenosine and kynurenine, which are key immune-suppressive metabolites. To understand which role these ASOs play within the tumor microenvironment, the Latvian Institute of Organic Synthesis will analyze the metabolite levels in independent cancer models after ASO-treatment. In parallel, the NGS core facility and the group of Hubert Hackl at the Institute of Bioinformatics (Medical University of Innsbruck) who are highly experienced in bulk and single-cell RNA expression analysis, will perform expression analysis and process expression data to characterize certain immune cell subsets in the TME of these models. By combining the metabolite panels and RNA expression pro the transnational scientific consortium aims to identify previously unknown biomarkers in order to predict the impact the various ASOS have on the disease course of cancer patients. The consortiums' scientific work is backed-up by Innoplexus, an AI & Blockchain powered virtual drug discovery company employing its proprietary platform, OntosightTM traverse the entire life science data universe including disease model experiments in combination with its world-leading patented AI technology to uncover novel biomarkers that could potentially have a role in tumor stratification. Alexander Gebauer, MD, PhD, CEO of Secarna Pharmaceuticals, said: "This newly founded research consortium provides us and our partners with the unique opportunity to work together to bring light into the operating principle of the tumor microenvironment and, therefore, identify novel biomarkers that correlate with specific tumor-induced immune resistance pathways. We at Secarna are looking forward to work together with our partners at Innoplexus, the Institute of Bioinformatics (Medical University of Innsbruck) and the Latvian Institute for Organic Synthesis to lay out the basis for individualized targeted therapy in the future." The consortium has applied for the project grant TRANSCAN-3 Sustained collaboration of national and regional programs in cancer research, funded by the European Commission under Horizon 2020 on the topic Next generation cancer immunotherapy: targeting the tumor microenvironment. About Secarna's proprietary drug discovery platform, LNAplusTM For discovering, testing and selecting antisense oligonucleotides (ASOs) for pre-clinical and clinical development, Secarna employs its proprietary, customized LNAplusTM drug discovery platform. LNAplusTM encompasses all aspects of drug discovery and pre-clinical development and has proven to be fast, reliable, scalable, efficient and to provide for a uniquely integrated workflow, enabling the discovery and development of novel antisense-based therapies.The platform includes the powerful proprietary OligofyerTM bioinformatics pipeline, a streamlined, high efficiency screening process including our proprietary LNA-Vit(r)oxTM safety test system as well as target-specific functional assays. Secarna's platform and ASOs have been validated by numerous in-house projects as well as in several academic and industry collaborations. About Secarna Pharmaceuticals GmbH & Co. KG Secarna Pharmaceuticals is the next generation antisense oligonucleotide (ASO) company addressing high unmet medical needs in the areas of immuno-oncology, immunology, as well as viral, neurodegenerative and cardiometabolic diseases. Secarna's mission is to maximize the performance and output of its proprietary LNAplusTM antisense oligonucleotide discovery platform, as well as to develop highly specific, safe, and efficacious best-in-class antisense therapies for challenging or currently undruggable targets. With over 15 development programs, including proprietary pipeline projects as well as partnered programs, we focus on targets in indications where antisense-based approaches have clear benefits over other therapeutic modalities, Secarna is the leading independent European antisense drug discovery and development company. About Latvian Institute of Organic Synthesis Latvian Institute of Organic Synthesis (LIOS) is a state research institute specializing in organic chemistry, pharmaceutical research, molecular biology, and bioorganic chemistry. LIOS is the leading drug discovery and development center in the Baltics and has more than 60 years of experience in drug design and technology development. IOS delivered 18 original and more than 70 generic medicines to its industrial partners. The mission of LIOS is to merge achievements of innovative academic research in organic chemistry and pharmacology with competence in applied research of medicinal chemistry, thus, contributing to the development of science in Latvia and quality of life of society. About the Institute of Bioinformatics (Medical University of Innsbruck) The Institute for Bioinformatics was established in 2010 as the latest member of the Biocenter at the Medical University of Innsbruck and it is dedicated to supporting basic research and teaching in bioinformatics and computational biology. The Institute for Bioinformatics is well equipped both for data processing and management as well as for computational analysis of a broad range of data types, including next-generation sequencing data, proteomics and metabolomics data, and image analysis. It has a state-of-the-art computational infrastructure, which is dedicated to bioinformatics analysis. A number of analytical pipelines, databases and software tools developed by the laboratory and others are installed and continuously maintained. The research of the Institute of Bioinformatics focuses on cancer immunology and aims at deciphering tumor-immune cell interaction by means of a combined computational-experimental approach. It specifically looks at the question of how the immune system shapes the mutation spectrum of the tumor, both during progression and after treatment, in patients with colorectal cancer. The institute uses tumor-derived organoids, perturbation experiments and multimodal analysis, including next-generation sequencing, phosphoproteomics and imaging mass cytometry to facilitate precision immuno-oncology. About Innoplexus AG Innoplexus is a leading global AI-based platform for drug discovery and development with over 250 employees and 120+ patent applications including 41 granted patents in artificial intelligence, machine learning, and blockchain technologies. Innoplexus' solutions can generate real-time insights from hundreds of terabytes of structured and unstructured private and public data, thereby, facilitating continuous, informed decision-making for its customer base at an unprecedented speed. Founded in 2015, Innoplexus AG is headquartered in Eschborn, Germany, with offices in Pune, India, as well as Iselin, and San Francisco, United States. Contact: Secarna Pharmaceuticals GmbH & Co. KG Alexander Gebauer, MD, PhD CEO alexander.gebauer@secarna.com Secarna Pharmaceuticals GmbH & Co. KG Am Klopferspitz 19 82152 Planegg/Martinsried Tel.: +49 (0)89 215 46 375 For media enquiries: Anne Hennecke/Vera Lang MC Services AG secarna@mc-services.eu Tel.: +49 (0)211.52 92 52 15 SOURCE: Secarna Pharmaceuticals GmbH & Co. KG View source version on accesswire.com:

Latvijas Gāze group showed an outstanding performance in first quarter of 2021. Last year’s strategic decision by JSC “Latvijas Gāze” to defer injected underground storage inventory to 2021 boosted gross profit margin amid continuous natural gas price rise. Additionally, significantly colder temperature increased JSC “Latvijas Gāze” sales and utilization of JSC “Gaso” distribution network. The rally is observed almost in all commodities on the back of economic recovery and supply constraints. Despite the fact that JSC “Latvijas Gāze” benefited from natural gas price rise in the first quarter, continuous commodity rally will pose a challenge for the remaining part of the year. The Group’s net turnover in the first quarter of 2021 was 75.2 million EUR, EBITDA* amounted to 28.3 million EUR and net profit was 24.7 million EUR. During first quarter of 2021, JSC “Latvijas Gāze” sold 4 181 GWh of natural gas to customers in Latvia and abroad. Compared to the same period in 2020, sales volumes has increased by 25%. Sales volumes to foreign counterparties accounted for 47% of the total sales volumes. The customer service centres of JSC “Latvijas Gāze” and JSC “Gaso” remain closed to visitors. Latvijas Gāze group will publish its unaudited consolidated financial statements for the second quarter of 2021 on August 25, 2021. *More detailed information on the alternative performance measures can be found on page 10 of the financial statements. Additional information:Romāns TjurinsVice President FinancePhone: + (371) 67 369 139E-mail: investor.relations@lg.lv Attachment