VAP-1

ECC5004/AZD5004 is an investigational oral small molecule GLP-1 receptor agonist licensed to AstraZeneca in November 2023BOSTON, Mass. and SHANGHAI, Oct. 23, 2024 (GLOBE NEWSWIRE) -- Eccogene, a clinical-stage biopharmaceutical company developing next-generation oral small molecule therapeutics for chronic cardiometabolic and inflammatory conditions, announced that it will receive a $60 million payment from AstraZeneca, which is being triggered by successfully achieving milestones related to the development of ECC5004/AZD5004 including the first patient dosed in the Phase 2b program. VISTA (NCT06579092) and SOLSTICE (NCT06579105) are two global Phase 2b multicenter trials assessing the efficacy and safety of ECC5004/AZD5004, administered orally, once daily, to participants who are obese or overweight with at least one weight-related comorbidity and type 2 diabetes, respectively. AstraZeneca licensed the global rights to ECC5004/AZD5004 from Eccogene in November 2023, for which the Company received an upfront payment of $185 million and can receive up to $1.825 billion in future milestones, as well as royalty payments. Eccogene retains co-development and co-commercialization rights to ECC5004/AZD5004 in China. “Obesity and its associated comorbidities affect over one billion people worldwide and continue to grow in prevalence. We are pleased to see ECC5004/AZD5004 – our internally discovered oral small molecule GLP-1 receptor agonist – advancing into Phase 2b clinical trials for obesity and type 2 diabetes. This is an important milestone for Eccogene, as it provides strong validation for our translational research platform and underscores the efficiency and effectiveness of our close collaboration with AstraZeneca,” said Jingye Zhou, Chief Executive Officer of Eccogene. Sharon Barr, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, commented: “Rapidly progressing AZD5004 is a priority, as novel solutions are needed for patients to address interrelated cardiometabolic disease and the serious risks associated with type 2 diabetes, obesity or overweight with comorbidities. The start of our two Phase 2b trials marks a significant milestone in our efforts to provide an alternative to current injectable therapies that can be offered as a monotherapy as well as in combination for addressing interrelated diseases.” Leveraging its translational research platform and deep understanding of metabolic disease pathways – in addition to ECC5004/AZD5004 – Eccogene discovered and is advancing a pipeline of next-generation oral therapeutics that can be used alone or in combination with GLP-1 receptor agonists. This includes the Company’s clinical-stage THR-β agonist and SSAO inhibitor – both of which are differentiated compounds, and when used in combination, can potentially help augment the efficacy of GLP-1 to address comorbidities of obesity. Eccogene is also advancing several innovative preclinical programs, such as a small molecule GIP receptor modulator. About EccogeneEccogene is a clinical-stage biopharmaceutical company developing next-generation oral small molecule therapeutics for chronic cardiometabolic and inflammatory conditions. Since its founding, Eccogene has been dedicated to discovering safer and more effective oral therapies that can be used alone or synergistically with a GLP-1 receptor agonist to treat conditions beyond obesity. The Company’s diverse pipeline of small molecule candidates leverages its world-class expertise in translational research, small molecule discovery, and a deep understanding of diabetes, weight loss, and cardiometabolic disease pathways. Eccogene’s oral small molecule GLP-1 receptor agonist, ECC5004/AZD5004, is a potentially best-in-class asset, which was licensed to AstraZeneca. Eccogene also has clinical programs underway that target THR-β and SSAO, as well as preclinical programs targeting proven pathways, such as GIP. For more information, please visit www.eccogene.com or follow the Company on LinkedIn. Media Contact Amy BonannoLyra Strategic Advisoryabonanno@lyraadvisory.com

A team has used neutron crystallography to image all of the atoms in a radical intermediate of a copper amine oxidase enzyme. They disclosed previously unknown details, such as precise conformational changes, that help to explain the enzyme's biochemistry. This work might help researchers engineer enzymes that facilitate unusual chemistry or are highly efficient at room temperature that are useful in chemical industry. When your wounds heal and your liver detoxifies a poison such as histamine you ingested, you can thank the class of enzymes known as copper amine oxidases for their assistance. Identifying the exact positions of the smallest hydrogen atoms in these enzymes is challenging with commonly used technologies, but is critical to engineering improved enzymes that exhibit unusual yet useful biochemical reactivity. Now, in a study recently published in ACS Catalysis, a team led by researchers at Osaka Medical and Pharmaceutical University and Osaka University has used neutron crystallography to image the atom-by-atom structure of a copper amine oxidase enzyme. This study provides unprecedented structural insights into the enzyme's biochemistry. Some copper amine oxidase enzymes exhibit unusual biochemistry, such as quantum tunneling, which enables otherwise inexplicably fast reaction rates. Although it is often challenging to determine the exact position of each hydrogen atom in the enzyme, such knowledge is important for designing corresponding artificial enzymes. Researchers commonly obtain the atom-by-atom structure of enzymes by X-ray crystallography. However, this technique obtains structural information by diffraction from electrons in the enzyme. Thus, it is insufficient for imaging hydrogen atoms, which generally contain only one electron. Neutron crystallography, which analyzes diffraction from atomic nuclei in the enzyme (all atoms have an atomic nucleus), is an alternative imaging technique that the researchers chose for their work. "There are pH-dependence, conformational change, and radical intermediate stabilization questions of our enzyme that X-ray crystallography in itself cannot fully explain," explains Takeshi Murakawa, lead author of the study. "Neutron crystallography is well-suited for answering these questions." The researchers obtained numerous insights. For example, they imaged the protonation/deprotonation state (related to the pH) of sites within the enzyme that are important for stabilizing radical species (i.e., especially reactive atoms that contain an unpaired electron). They also characterized the motions of the enzyme's topaquinone cofactor -- sliding, upward tilting, and half-rotation -- that facilitate single-electron transfer within the enzyme. "We disclose binding of a second molecule of high-affinity amine substrate during the enzymatic reaction, a previously unknown event in the enzyme active site," says Toshihide Okajima, senior author. "X-ray crystallography misses such insights." This work has provided previously undisclosed structural details in a copper amine oxidase enzyme that has many functions in biochemical metabolism. Revealing the exact position of the hydrogen atoms in the enzyme helps to explain its efficiency at physiological temperatures and pressures. In the future, researchers might apply these insights to designing artificial enzymes that function used in the chemical industry.

Eccogene’s ECC5004 has been designed to treat obesity and type 2 diabetes. Credit: abolukbas / Shutterstock.com. Clinical-stage biotechnology firm Eccogene has raised $25.23m (CNY180m) in a Series B financing round to support the development of its clinical-stage metabolic pipeline. Co-led by Zhangjiang Healthcare Venture Capital and New Alliance Capital, the financing round has seen participation from existing investors Qingsong Capital, Delos Capital and Oriza Seed Capital. Recommended Reports Reports Clinical Trials - The Expanding Landscape of Regenerative Medicine GlobalData Reports LOA and PTSR Model - Trecondyv in Hematopoietic Stem Cell Transplantation GlobalData View all New investors Elikon Venture, YuFu Investment, Rockbleu Capital and Huajin Capital have also participated in the financing round. Eccogene’s clinical pipeline includes a once daily, low-dose, small molecule GLP-1 receptor agonist (GLP-1RA), ECC5004, designed for type 2 diabetes (T2D) and obesity. The therapy is being evaluated in a US Phase I clinical trial in T2D patients and healthy participants. ECC4703 is a THRβ full agonist, now being assessed in a US Phase I trial in patients with elevated LDL and healthy participants. In preclinical trials, the therapy showed superiority over partial agonist MGL-3196 and robust efficacy in pre-clinical NASH [a form of non-alcoholic fatty liver disease that involves inflammation of the liver and liver damage, in addition to fat in the liver] and dyslipidemia models. ECC0509 is a peripherally distributed SSAO/VAP-1 inhibitor that is nearing completion of a Phase I clinical trial. Eccogene also intends to use the proceeds from the financing to further advance its preclinical programmes to treat metabolic and immunological diseases. Eccogene CEO Jingye Zhou stated: “We are thrilled that the series B financing enables us to advance clinical trials of a potentially best-in-class small molecule GLP-1RA to treat obesity, diabetes and related complications, and to further develop several highly differentiated assets for metabolic and immunological diseases. “This financing brings us a step closer to providing clinical benefits to hundreds of millions of patients affected by obesity, T2D and NASH globally.”