Posters

View Poster Carat

AXA1125-Associated Metabolic Profile Changes Are Predictive of Observed Reductions in Liver Fat Content in NAFLD

AASLD Liver Meeting 2021 | Nov. 2021

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is prevalent in >25% of the global population and in 50% to 90% of obese adults. Once nonalcoholic steatohepatitis (NASH) occurs, there may be progression to cirrhosis. Patients with NASH may benefit from approaches that concurrently address multiple metabolic and fibroinflammatory pathways; however, at present, there are no approved…

Carat View Poster

Posters

View Poster Carat

AXA1665 Shows Dose-Dependent Alterations in Metabolic Profile, Including Reduction of Non-dosed Aromatic Amino Acids, That Differentiate it From Protein Supplement in Healthy Subjects

AASLD Liver Meeting 2021 | Nov. 2021

INTRODUCTION: Dysregulated nitrogen metabolism in cirrhosis, i.e., elevated plasma ammonia and amino acid imbalance (decreased branched chain amino acids [BCAAs] and elevated aromatic amino acids [ArAAs]), is associated with complications of sarcopenia and cognitive dysfunction. Impaired hepatic detoxification of ammonia leads to accelerated catabolism of BCAAs in skeletal muscle. This cascade contributes to the development…

Carat View Poster

Publications

View Paper Carat

Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease

American Journal of Gastroenterology | August 2021

INTRODUCTION: AXA1125 and AXA1957 are novel, orally administered endogenous metabolic modulator compositions, specifically designed to simultaneously support multiple metabolic and fibroinflammatory pathways associated with nonalcoholic fatty liver disease (NAFLD). This study assessed safety, tolerability, and biologic activity of AXA1125 and AXA1957 in NAFLD. AXA1125 and AXA1957 in NAFLD. Methods: In this multicenter, 16-week, placebo-controlled, single-blind,…

Carat View Paper

Posters

View Poster Carat

LIVRQNac (AXA1125) Enhances Insulin Sensitivity in Primary Human Hepatocytes and in Subjects With NAFLD and T2D

American Diabetes Association 81st Scientific Sessions | June 2021

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a multifactorial condition that is mediated by dysregulated metabolic and fibroinflammatory pathways. Insulin resistance, commonly manifested as type 2 diabetes (T2D), is an important driver of NAFLD and targeting these metabolic pathways is a potential therapeutic strategy.  Endogenous metabolic modulators (EMMs), a broad set of physiologically intrinsic molecules…

Carat View Poster

Publications

View Paper Carat

A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models

Scientific Reports | June 2021

ABSTRACT Nonalcoholic steatohepatitis (NASH) is a complex metabolic disease of heterogeneous and multifactorial pathogenesis that may benefit from coordinated multitargeted interventions. Endogenous metabolic modulators (EMMs) encompass a broad set of molecular families, including amino acids and related metabolites and precursors. EMMs often serve as master regulators and signaling agents for metabolic pathways throughout the body…

Carat View Paper

Presentations

View Presentation Carat

A novel, precision-engineered amino acid composition, AXA1665, is safe, well-tolerated and improves neurocognition and physical function in Child-Pugh A and B subjects.

DDW 2021 | May 2021

INSTITUTIONS (ALL): 1. Virginia Commonwealth University, Richmond, VA, United States. 2. Axcella Health Inc., Cambridge, MA, United States. 3. Panax Clinical Research, Miami, FL, United States. 4. Ann Storck Centre, Fort Lauderdale, FL, United States. 5. Orange County Research Centre, Tustin, CA, United States. 6. Texas Liver Institute, San Antonio, TX, United States. 7. Pittsburgh…

Carat View Presentation

Posters

View Poster Carat

Mechanistic Insights Into AXA1125, a Novel Endogenous Metabolic Modulator Composition, Targeting Multiple NASH Drivers

Abstract 22 | NASH-TAG 2021

INTRODUCTION: Recent advances in network biology have assisted in unraveling the complex pathophysiological processes underlying nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH) and cirrhosis1 The close inter-connectivity of the contributory molecular pathways suggests that effective pharmacotherapy may require a coordinated multitargeted approach Per this premise, endogenous metabolic modulators (EMMs) have…

Carat View Poster

Posters

View Poster Carat

Safety, Tolerability, and Biological Activity of AXA1125 and AXA1957 in a Prospective 16-Week Randomized, Placebo-Controlled Study in Subjects With NAFLD With and Without Type 2 Diabetes

Abstract 1694 | The Liver Meeting® 2020, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is associated with a spectrum of histologic manifestations, including isolated steatosis, steatohepatitis, fibrosis, and cirrhosis. Patients with complex multifactorial diseases like NAFLD and nonalcoholic steatohepatitis (NASH) may benefit from approaches that concordantly address multiple metabolic and fibroinflammatory pathways. Endogenous metabolic modulators (EMMs) encompass a broad set of molecular families…

Carat View Poster

Posters

View Poster Carat

Biological Activity of AXA1125 and AXA1957 on Glucose, Insulin, HOMA-IR, and HbA1c and Measures of Liver Fat and Fibroinflammation in a Prospective 16-Week Randomized, Placebo-Controlled Study in Subjects With NAFLD and Type 2 Diabetes

Abstract 1663 | The Liver Meeting® 2020, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is multifactorial, mediated by dysregulated metabolic and fibroinflammatory pathways. Because NAFLD and type 2 diabetes (T2D) have a well-established bidirectional link, with insulin resistance serving as a common metabolic driver, targeting insulin resistance is a potential strategy for managing NAFLD. Endogenous metabolic modulators (EMMs) encompass a broad set of…

Carat View Poster

Publications

View Paper Carat

Endogenous Metabolic Modulators: Emerging Therapeutic Potential of Amino Acids

iScience | September 2020

INTRODUCTION: Multifactorial disease pathophysiology is complex and incompletely addressed via existing targeted pharmacotherapies. Amino acids (AAs) and related metabolites and precursors are a class of endogenous metabolic modulators (EMMs) that have diverse biological functions and, thus, have been explored for decades as potential multifactorial disease treatments. Here, we review the literature on this class of…

Carat View Paper

Posters

View Poster Carat

Multifactorial Effects of AXA1125 and AXA1957 Observed on Markers of Metabolism, Inflammation and Fibrosis: A 16-Week Randomized Placebo-Controlled Study in Subjects With Nonalcoholic Fatty Liver Disease (NAFLD) With and Without Type 2 Diabetes (T2D)

The Digital International Liver Congress | August 27 - 29, 2020

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is associated with a spectrum of histologic manifestations, including simple steatosis, steatohepatitis, fibrosis, and cirrhosis • Because multiple metabolic and fibroinflammatory pathways are dysregulated in NAFLD and nonalcoholic steatohepatitis (NASH), patients may benefit from approaches that support multiple pathways related to normal health processes • Endogenous metabolic modulators (EMMs)…

Carat View Poster

Publications

View Paper Carat

Safety, Tolerability, and Physiological Effects of AXA1665, a Novel Composition of Amino Acids, in Subjects With Child–Pugh A and B Cirrhosis

Clinical and Translational Gastroenterology | August 2020

INTRODUCTION: AXA1665 is a novel investigational amino acid (AA) composition specifically designed to impact AA imbalance, ammoniagenesis, and dysregulated anabolic activity associated with cirrhosis. METHODS: This 2-part study examined AXA1665 effects on safety, tolerability, and hepatic/muscle physiology in subjects with Child–Pugh A and B cirrhosis. Part 1 established plasma ammonia and AA concentration baselines with…

Carat View Paper

Publications

View Paper Carat

A Novel Amino Acid Composition Ameliorates Short-Term Muscle Disuse Atrophy in Healthy Young Men

Frontiers in Nutrition | July 10, 2019

INTRODUCTION: Skeletal muscle disuse leads to atrophy, declines in muscle function, and metabolic dysfunction that are often slow to recover. Strategies to mitigate these effects would be clinically relevant. In a double-blind randomized-controlled pilot trial, we examined the safety and tolerability as well as the atrophy mitigating effect of a novel amino acid composition (AXA2678),…

Carat View Paper

Publications

View Paper Carat

Nutrition and Nonalcoholic Fatty Liver Disease: Current Perspectives

Gastroenterology Clinics of North America | March 2020

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) pathogenesis and progression are complex, heterogeneous, and multifactorial. The human diet typically contains thousands of bioactive molecules that orchestrate a variety of metabolic and signaling processes in health and disease, comprising a natural combination approach. Although food composition varies widely, cumulative evidence suggests that specific dietary macronutrients and micronutrients…

Carat View Paper

Publications

View Paper Carat

The Metabolic Basis of Nonalcoholic Steatohepatitis

Endocrinology, Diabetes & Metabolism, Special Issue: NASH | October 2020

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and is associated with significant morbidity and mortality worldwide, with a high incidence in Western countries and non‐Western countries that have adopted a Western diet. NAFLD is commonly associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular…

Carat View Paper

Presentations

View Presentation Carat

Unique Composition of Endogenous Metabolic Modulators Reprograms Metabolic State and Impacts Markers of Inflammation and Fibrosis in NAFLD/NASH Cell Model Systems

Keystone Symposia | January 22-24, 2019

INTRODUCTION: Dysregulation of metabolic, inflammation and fibrotic pathways are linked to NAFLD progression. Effective therapies may require coordinated combinatorial approach to address multifactorial pathology. One potential modality is via endogenous molecules, such as amino acids (AAs), which when optimally combined can elicit meaningful effects. AXA1125, comprised of 6 AAs (LIVRQNac), designed to target liver function,…

Carat View Presentation

Presentations

View Presentation Carat

Development of an in vitro platform to predict and screen combinations of endogenous metabolic modulators capable of influencing muscle physiology

International Conference on Frailty and Sarcopenia Research (ICFSR) | March 11-13,2020

INTRODUCTION: Dysregulated metabolism contributes to muscle wasting which results in decreased quality of life and morbidity and mortality in aging and disease. We previously published that AXA2678, a composition of Endogenous Metabolic Modulators (EMMs) anchored by amino acids (AA), promotes maintenance of muscle mass, prevents muscle fat accumulation, decreases pro-inflammatory cytokines and promotes myogenic myokines…

Carat View Presentation

Posters

View Poster Carat

A Novel Composition of Endogenous Metabolic Modulators, AXA4010, Impacts Adhesion, Inflammation, and RBC Membrane Deformability in Preclinical Models of Sickle Cell Disease

American Society of Hematology (ASH) | December 7-10, 2019

INTRODUCTION: In sickle cell disease (SCD), red blood cell (RBC) sickling propagates hemolysis, inflammation, vascular and endothelial injury with associated disruption in metabolic pathways including nitric oxide depletion, oxidative stress and an increased anabolic and energetic demand due to high RBC turnover. These metabolic functions highlight the role of amino acid biology in blood health…

Carat View Poster

Posters

View Poster Carat

AXA1665, a Defined Composition of Endogenous Metabolic Modulators, But Not Dietary Protein Improves the Dysregulated Amino Acid Metabolism and Ammonia Disposal in Child–Pugh A and B Subjects

American Association for the study of liver disease (AASLD) | November 8-12, 2019

INTRODUCTION: Dysregulated nitrogen (N) handling due to impaired ureagenesis and amino acid (AA) metabolism results in a distinct plasma AA profile (eg ↓BCAA, ↑AAA) with hyperammonemia and muscle wasting in cirrhosis. While protein supplementation is standard‐of‐care for cirrhotic patients, it carries the risk of hyperammonemia and hepatic encephalopathy due to the underlying defective N metabolism…

Carat View Poster

Posters

View Poster Carat

Mechanistic insights into the multimodal effects of AXA1125 in T2D subjects with NAFLD

American Association for the study of liver disease (AASLD) | November 8-12, 2019

INTRODUCTION: Convergent dysregulation of metabolism, inflammation, and fibrosis appears to be central to NASH pathogenesis. Previously [Hepatology 68(1) Suppl, pg 67A: #106], we showed AXA1125, a unique composition of amino acids (LIVRQNac), positively impacted lipotoxicity, insulin resistance, inflammation and fibrosis markers in T2D subjects with NAFLD as evidenced by reductions in liver fat, HOMA‐IR, ALT,…

Carat View Poster

Posters

View Poster Carat

AXA1665, a Novel Composition of Amino Acids, Restores the Dysregulated Amino Acid Profile, Lowers Ammonia, and Improves Body Composition and Function in Child–Pugh Class A and B Subjects

The European Association for the Study of the Liver (EASL) | April 10-14, 2019

INTRODUCTION: Sarcopenia has emerged as an independent risk factor for important clinical outcomes in cirrhosis, including hepatic encephalopathy (HE). It is closely linked to protein-malnutrition and perturbation in amino acid metabolism. A late evening snack (LES), considered part of routine care, appears to improve quality-of-life parameters in cirrhotic patients. While protein supplementation is advised, it…

Carat View Poster