AXA1125 / Axcella - LARVOL DELTA

ADVANCING THE MULTI-TARGETED MECHANISMS OF ACTION OF A MITOCHONDRIAL ACTIVATOR (AXA-1125) FOR TREATING NASH USING A QUANTITATIVE SYSTEMS PHARMACOLOGY MODEL (AASLD 2023) - P=N/A | "NAFLDsym, a QSP model of NAFLD/NASH, was used to investigate the combination of mechanisms playing a role in AXA-1125, a NASH therapeutic candidate. Here, NAFLDsym simulations support the following mechanisms contributing to the clinical response of AXA-1125: incretin effects, AMPK-responsive enzyme expression, antioxidant-mediated reduction of lipotoxicity, and inhibition of TNFα production. This works independently recapitulates previously published MoA findings, including AXA-1125 as a mitochondrial activator, and predicts novel contributions which require additional work to be validated and expanded upon."

Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Inflammation • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • AMPK • TNFA

Efficacy and Tolerability of AXA1125, an Endogenous Metabolic Modulator Composition, in Fatigue-predominant Long COVID: A Randomized, Double-blind, Placebo-controlled Study (ATS 2023) - P2 | "AXA1125 is a composition of leucine, isoleucine, valine, arginine, glutamine, and N-acetylcysteine. AXA1125 is well-tolerated and, if confirmed, these data suggest it is the first oral therapy to reduce Long COVID fatigue measured using a validated instrument over 4 weeks."

Clinical • Fatigue • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study. (PubMed, EClinicalMedicine) - P2 | "Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID. Axcella Therapeutics."

Journal • P2a data • Fatigue • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

"Different tests are in progress, such as Ph with @Vickyvdtogt, Amoxiclav @remissionbiome, Axa 1125, the Telemilab, or the protocol of @brucep13 etc" (@AnthonyBou1)

Clinical

"Interesting. I'll take a look at AXA1125's bibliography." (@JML21071664)

Efficacy and tolerability of AXA1125 (endogenous metabolic modulator) in fatigue-predominant long COVID: a randomised, double-blind, controlled study (ECCMID 2023) - No abstract available

Clinical • Late-breaking abstract • Fatigue • Novel Coronavirus Disease

"Für mich eines der Highlights vom #ECCMID2023: Plazebo-kontrollierte doppelt-blinde Studie der @UniofOxford zu Post-COVID Fatigue. Signifikante Verbesserung der Fatigue durch AXA1125 (ein Peptide mit Metabolismus-modulierenden Eigenschaften)." (@Sander_Lab)

Fatigue • Novel Coronavirus Disease

[VIRTUAL] 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) (EASL-ILC-I 2020) - P=N/A | "AXA1125 and AXA1957 were safe, well tolerated, and led to clinically relevant multifactorial effects. These EMM compositions represent a novel mode of action with the potential to simultaneously address NASH and key comorbidities, including insulin sensitivity."

Clinical • Late-breaking abstract • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus

AXA1125, an endogenous metabolic modulator composition, improves long COVID fatigue, vascular biology and mitochondrial energetics: findings from a Phase 2a placebo-controlled clinical trial (ECCMID 2023) - No abstract available

Clinical • P2a data • Fatigue • Novel Coronavirus Disease

"$AXLA Axcella Announces Regulatory Path to Registration of AXA1125 for Long COVID Fatigue https://t.co/wRPDIzLz5I" (@stock_titan)

Fatigue • Novel Coronavirus Disease

IDENTIFYING PREDICTIVE PLASMA PROTEOMIC BIOMARKERS FOR CLINICAL RESPONSE TO AXA1125, AN ENDOGENOUS METABOLIC MODULATOR (EMM) COMPOSITION BEING DEVELOPED FOR THE TREATMENT OF NAFLD/NASH (AASLD 2022) - P=N/A | "As a part of our systems biology platform, we explored plasma protein biomarkers to predict responders to AXA1125 treatment, a novel endogenous metabolic modulator composition of 5 specific amino acids and n-acetylcysteine, using proton density fat fraction (PDFF) improvement >30%, associated with histologic response in NASH, as a metric. This work demonstrates a proof-of-concept for predicting subjects with a high response to AXA1125. Models achieved good performance at Week 16. Different protein predictors may reflect biological pathways relevant to an earlier PDFF improvement."

Biomarker • Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • PTEN

AXA1125-201: Efficacy, Safety, Tolerability of AXA1125 in Fatigue After COVID-19 Infection (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: Axcella Health, Inc | Active, not recruiting ➔ Completed

Trial completion • Fatigue • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

LIVRQNac increases fatty acid oxidization in a primary human hepatocyte model of non-alcoholic steatohepatitis (EASL-ILC 2022) - "LIVRQNac, an EMM composition of 5 amino acids (AA) and n-acetylcysteine (Nac), decreased liver fat accumulation (in vivo and in vitro) by reducing triglyceride accumulation...On day 3, cells were incubated in custom media containing 500 μM carnitine,10 μg/ml insulin, EGF,1 μM dexamethasone, and custom AA concentrations (as in healthy human plasma) with and without LIVRQNac (10X and 30X) and with lipotoxic insult (saturated free fatty acids [2:1 oleate: palmitate] and tumor necrosis factor alpha (1 ng/ml)... Increases in labeled palmitoylcarnitine, acetylcarnitine and acetyl-coA reflected an increase in FAO in PHHs treated with LIVRQNac. Consistently, therewas an increase in total and labelled β- hydroxybutyric acid in LIVRQNac-treated cells indicating an increase in ketogenesis. These data support a mechanism for AXA1125’s clinical effect of decreasing liver fat, by increasing ketogenesis and increasing FAO."

Addiction (Opioid and Alcohol) • Hepatology • Non-alcoholic Steatohepatitis • Oncology • EGF • TNFA

AXA1125-201: Efficacy, Safety, Tolerability of AXA1125 in Fatigue After COVID-19 Infection (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Axcella Health, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Fatigue • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy, Safety, Tolerability of AXA1125 in Fatigue Predominant PASC (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: Axcella Health, Inc

Clinical • New P2 trial • Fatigue • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • PCR

[VIRTUAL] AXA1125-ASSOCIATED METABOLIC PROFILE CHANGES ARE PREDICTIVE OF OBSERVED REDUCTIONS IN LIVER FAT CONTENT IN NAFLD (AASLD 2021) - P=N/A | "AXA1125 is associated with a distinct metabolic signature in fasting plasma from subjects with NAFLD that is predictive of MRI-PDFF reductions, including significant changes across dosed and non-dosed AAs, and polar metabolites. Our findings add to a growing body of data suggesting an association between the metabolic profile of AXA1125 and MRI-PDFF improvements, consistent with the proposed multifactorial metabolic impact of AXA1125 ."

Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • MRI

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) (EASL-NAFLD 2021) - No abstract available.

AXA1125 safe, well tolerated up to 16 weeks in patients with NAFLD (Healio) - '"[Our] systematic characterization of specific [endogenous metabolic modulator (EMM)] compositions in NAFLD adds to the depth of knowledge on the safety and physiologic activity of EMMs and highlights that specificity of EMM composition matters for optimal effects,' Stephen A. Harrison...'Our findings support the potential of a novel EMM composition, AXA1125, to simultaneously address the multifactorial pathogenesis of NAFLD/[nonalcoholic steatohepatitis (NASH)], their key comorbidities, representing a unique modality with a coordinated multitargeted mechanism of action without major safety or tolerability issues.'"

Media quote

Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease. (PubMed, Am J Gastroenterol) - "Both compositions showed multitargeted activity on relevant NAFLD pathways. AXA1125 demonstrated the greatest activity over 16 weeks, warranting continued clinical investigation in nonalcoholic steatohepatitis subjects."

Clinical • Journal • Diabetes • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus • KRT18 • MRI

[VIRTUAL] LIVRQNac (AXA1125) Enhances Insulin Sensitivity in Primary Human Hepatocytes and in Subjects with NAFLD and T2D (ADA 2021) - P=N/A | "This concordant multifactorial biologic activity, including the effects on glucose homeostasis, suggests a potential enhanced impact of AXA1125 in NAFLD subjects with diabetes that warrants further investigation."

Clinical • Diabetes • Metabolic Disorders • Non-alcoholic Fatty Liver Disease

[VIRTUAL] 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 (AASLD 2020) - P=N/A | "AXA1125 and AXA1957 were safe, well tolerated, and showed multitargeted activity on metabolic and fibroinflammatory pathways of NASH, with AXA1125 showing greater activity in subjects with and without T2D. AXA1125 will be evaluated in studies for treatment of NASH in adults and pediatric populations."

Clinical • Diabetes • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Pediatrics • Type 2 Diabetes Mellitus • MRI • PRO-C3

[VIRTUAL] 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 (AASLD 2020) - P=N/A | "Multitargeted activity for both EMM compositions, particularly AXA1125, was observed in T2D subjects. AXA1125 improved glucose homeostasis without weight change and showed concordant improvement in liver fat and fibroinflammation markers. The potential for AXA1125 to modulate insulin resistance, a critical driver of nonalcoholic steatohepatitis (NASH) pathogenesis, supports investigation in IND–clinical studies for adults and children with NASH."

Clinical • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus • MRI

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 (NASH-TAG 2021) - P=N/A | "AXA1125 and AXA1957 were safe, well tolerated, and showed multitargeted activity on metabolic and fibroinflammatory pathways of NASH, with AXA1125 showing greater activity in subjects with and without T2D. AXA1125 will be evaluated in studies for treatment of NASH in adults and pediatric populations. Abstract accepted by the AASLD for presentation at The Liver Meeting Digital Experience,"

Clinical • Diabetes • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Pediatrics • Type 2 Diabetes Mellitus • MRI • PRO-C3

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, PLACEBOCONTROLLED STUDY IN SUBJECTS WITH NAFLD AND TYPE 2 DIABETES (NASH-TAG 2021) - P=N/A | "Multitargeted activity for both EMM compositions, particularly AXA1125, was observed in T2D subjects. AXA1125 improved glucose homeostasis without weight change and showed concordant improvement in liver fat and fibroinflammation markers. The potential for AXA1125 to modulate insulin resistance, a critical driver of nonalcoholic steatohepatitis (NASH) pathogenesis, supports investigation in IND– clinical studies for adults and children with NASH."

Clinical • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus • MRI

Safety, Tolerability, and Efficacy of AXA1125 in NASH With Fibrosis (clinicaltrials.gov) - P2; N=273; Recruiting; Sponsor: Axcella Health, Inc

Clinical • New P2 trial • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • MRI