公表論文・ポスター発表資料

Efficacy and safety of PXL770, a direct AMP kinase activator, for the treatment of non-alcoholic fatty liver disease (STAMP-NAFLD): a randomised, double-blind, placebo-controlled, Phase 2a study

Ken Cusi, et al. Lancet Gastroenterol Hepatol — September 2021

Direct AMPK Activation Corrects NASH in Rodents Through Metabolic Effects and Direct Action on Inflammation and Fibrogenesis

Pascale Gluais-Dagorn, et al. Hepatol Commun — 2021

Human Proof-of-Concept in NAFLD Patients with PXL770, a Novel First-in-Class Direct AMP-Kinase Activator (mentioné par David)

Ken Cusi et al. — March 2021, NASH-TAG, Oral presentation

Therapeutic efficacy potential of PXL770 - a novel direct AMPK-activator and PXL065 – deuterium-stabilized R-pioglitazone - for X-linked adrenoleukodystrophy

Jaspreet Singh, et al. — November 2020, ALD Connect Annual Meeting

PXL770, a Novel Direct AMP-activated Protein Kinase Activator Produces Greater Efficacy when Combined with Other Key Therapeutic Mechanisms Targeting NASH

Pierre-Axel Monternier, et al. — November 2020, AASLD (American Association for the Study of Liver Diseases)

PXL770, A New Direct AMP Kinase Activator and Potential NASH Therapeutic, Produces Anti-inflammatory Effects in Mouse Liver and Adipose Tissue and in Human Immune Cells

Pascale Gluais-Dagorn, et al. — November 2020, AASLD (American Association for the Study of Liver Diseases)

PXL770, a Novel Direct AMP-activated Protein Kinase Activator, Improves Hepatic Mitochondrial Function in a Rodent NASH Model

Pierre-Axel Monternier, et al. — November 2020, AASLD (American Association for the Study of Liver Diseases)

Chronic Treatment With The Direct AMP Kinase Activator PXL770 Improves Cardiac And Renal Function In Diabetes Related Cardiorenal Syndrome

Y. Stephan et al. — September 2020, EASD (European Association for the Study of Diabetes)

PXL770, a new direct AMP-activated protein Kinase (AMPK) activator, demonstrates anti-inflammatory and anti-fibrogenic effects in DIO-NASH mice model

Pascale Gluais-Dagorn et al. — February 2020, Global NASH Congress, Oral presentation

PXL770, a New Direct AMP Kinase Activator, Acting on the Adipose Tissue and the Liver, Demonstrates Promising Effects for Treatment of Non-Alcoholic Steatohepatitis

Pascale Gluais-Dagorn et al. — November 2018, AASLD (American Association for the Study of Liver Diseases), San Francisco, USA

PXL770, a direct AMPK activator, shows favorable cardiac safety profile

Sophie Hallakou-Bozec et al. — October 2018, International Meeting on AMPK, Toronto, Canada

PXL770, a direct AMPK activator for the treatment of NASH, shows a favorable PK, tolerability and safety profile in humans

Sandrine Perrimond-Dauchy et al. — October 2018, International Meeting on AMPK, Toronto, Canada

PXL770, a new direct AMP Kinase activator, demonstrates promising effects for treatment of non-alcoholic steatohepatitis

Pascale Gluais-Dagorn et al. — February 2018, Global NASH Congress, London, UK

PXL770, a novel direct AMPK activator, improves metabolic disorders in a diet-induced mouse model of obesity and diabetes EASD,

Sébastian Bolze et al. — September 2016, EASD (European Association for the Study of Diabetes), Munich, Germany

PXL770, a Novel Direct AMPK Activator, Inhibits Hepatic de novo Lipogenesis for the Treatment of Metabolic Disorders EASD

Sophie Hallakou-Bozec et al. — September 2016, EASD (European Association for the Study of Diabetes), Munich, Germany

PXL770 Demonstrates Therapeutic Potential as a New Direct AMP Kinase Activator WCIRDC

Sophie Hallakou-Bozec et al. — November 2015, WCIRDC (World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease), Los Angeles, USA

PXL065 (Deuterium-Stabilized R-enantiomer of pioglitazone) Reduces Liver Fat Content and Improves Liver Histology without PPAR-mediated Side Effects in Patients with NASH: Analysis of a 36 Week Placebo-Controlled Phase 2 Trial (DESTINY-1)

Stephen A. Harrison, et al. — November 2022, AASLD The Liver Meeting

Therapeutic potential of deuterium-stabilized(R)-pioglitazone — PXL065 — for X-linkedadrenoleukodystrophy

Pierre-Axel Monternier, et al. — May 2022, The Journal of Inherited Metabolic Disease (JIMD)

Human Pharmacokinetics and NASH Development Strategy for PXL065 – Deuterium-Stabilized (R)-Pioglitazone

Sebastien Bolze, et al. — March 2021, NASH-TAG

Deuterium‐Stabilized (R)‐Pioglitazone (PXL065) Is Responsible for Pioglitazone Efficacy in NASH yet Exhibits Little to No PPARγ Activity

Jacques, V., et al. Hepatol Commun — 2021

Therapeutic efficacy potential of PXL770 - a novel direct AMPK-activator and PXL065 – deuterium-stabilized R-pioglitazone - for X-linked adrenoleukodystrophy

Jaspreet Singh, et al. — November 2020, ALD Connect Annual Meeting

Phase 1b Study of PXL065 (Deuterium-Stabilized R-Pioglitazone), a Novel NASH Candidate, Predicts 15 mg Equivalent to 45 mg Actos®

Sebastien Bolze, et al. — November 2020, AASLD (American Association for the Study of Liver Diseases)

Deuterium-Enabled Chiral Switching (DECS) Yields Chirally Pure Drugs from Chemically Interconverting Racemates

DeWitt, S., et al. ACS Med Chem Lett — 2020

Phase 1 Study of PXL065 Confirms Dose-Proportionality & Stabilization of the Preferred Stereoisomer (R-Pioglitazone) for the Treatment of NASH

Bolze et al. — November 2019, AASLD (American Association for the Study of Liver Diseases), Boston, MA, USA

PXL065, Pioglitazone (pio), and Thiazolidinediones (TZDs): Unraveling Pio’s superior efficacy for NASH and role of stereoisomers

Sheila DeWitt et al. — March 2019, NASH-TAG Oral presentation

Safety, Tolerability & PK of PXL065*, the Stabilized R-Stereoisomer of Pioglitazone: A Mitochondrial Function Modulator for NASH without PPARγ Agonism & Related Side Effects

Vincent Jacques et al. — November 2018, AASLD (American Association for the Study of Liver Diseases), San Francisco, USA

DRX-065: A Novel Mitochondrial Modulator for NASH Pharmacokinetic (PK) Results & Modeling from Phase 1 Study

Vincent Jacques et al. — March 2018, NASH-TAG Poster

DRX-065: A Novel Mitochondrial Modulator

Sheila DeWitt et al. — March 2018, NASH-TAG Oral presentation

The Deuterated (R)-Enantiomer of Pioglitazone as a Nonalcoholic Steatohepatitis (NASH) drug candidate: Results from Diet-Induced Rodent NASH Models and Phase I

Sheila DeWitt et al. — August 2018, ACS (American Chemical Society) Oral presentation

Deuterated Drug Molecules: Focus on FDA-Approved Deutetrabenazine Published as part of the Biochemistry series "Biochemistry to Bedside"

DeWitt, S.H., et al. Biochemistry — 2018

Efficacy of DRX-065, the stabilized R-enantiomer of pioglitazone (pio), in choline-deficient (CD) and methionine/choline-deficient (MCD) diet mouse models of nonalcoholic steatohepatitis (NASH)

Sharon C. Cheetham et al. — November 2017, AASLD Poster

Efficacy of DRX-065, the stabilized R-enantiomer of pioglitazone (pio), in choline-deficient (CD) and methionine/choline-deficient (MCD) diet mouse models of nonalcoholic steatohepatitis (NASH)

Sharon C. Cheetham et al. — November 2016, AASLD (American Association for the Study of Liver Diseases), Nottingham, UK

Discovery of DRX-065: Characterizing the non-PPARγ, mitochondrial function modulation and anti-inflammatory activity of thiazolidinedione (TZD) enantiomers using deuterium (MEDI 274)

Anthony W. Czarnik et al. — August 2016, ACS Oral presentation

Efficacy and Safety of Imeglimin add-on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES 3): A randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period

Dubourg, J., et al. Diabetes Obes Metab — 2022

Long-term Safety and Efficacy of Imeglimin as monotherapy or in combination with existing antidiabetic agents in Japanese patients with type 2 diabetes (TIMES 2): A 52-week, open-label, multicentre phase 3 trial

Dubourg, J., et al. Diabetes Obes Metab — 2021

The mechanism by which imeglimin inhibits gluconeogenesis in rat liver cells

Vial, G., et al. Endocrinol Diabetes Metab — 2021

Mechanism of Action of Imeglimin: A Novel Therapeutic Agent for Type 2 Diabetes

Hallakou-Bozec, S., et al. Diabetes Obes Metab — 2021

Imeglimin Amplifies Glucose-stimulated Insulin Release From Diabetic Islets Via a Distinct Mechanism of Action

Hallakou-Bozec, S., et al. PLoS One — 2021

Efficacy and Safety of Imeglimin in Japanese Patients with Type 2 Diabetes: A 24-week, Randomized, Double-blind, Placebo-controlled, Dose-ranging Phase 2b trial

Dubourg, J., et al. Diabetes Obes Metab — 2021

Efficacy and Safety of Imeglimin Monotherapy Versus Placebo in Japanese Patients With Type 2 Diabetes (TIMES 1): A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 3 Trial

Dubourg, J., et al. Diabetes Care — 2021

Long-term treatment with imeglimin as add-on to oral antidiabetes therapy in Japanese patients with type 2 diabetes (TIMES 2) (Phase 3)

J. Dubourg et al. — September 2020, EASD (European Association for the Study of Diabetes)

Efficacy And Safety Of Imeglimin In Combination With Insulin In Japanese Patients With Type 2 Diabetes: Results of TIMES 3 Trial (Phase 3)

J. Dubourg et al. — September 2020, EASD (European Association for the Study of Diabetes)

Short-and Long-term Administration of Imeglimin Counters Cardiorenal Dysfunction in a Rat Model of Metabolic Syndrome

Lachaux, M., et al. Endocrinol Diabetes Metab — 2020

Imeglimin Preserves Islet β-cell Mass in Type 2 Diabetic ZDF Rats

Hallakou-Bozec, S., et al. Endocrinol Diabetes Metab — 2020

Imeglimin Does Not Induce Clinically Relevant Pharmacokinetic Interactions When Combined with Either Metformin or Sitagliptin in Healthy Subjects

Fouqueray, P., et al. Clin Pharmacokinet — 2020

Absence of QTc Prolongation in a Thorough QT Study with Imeglimin, a First in Class Oral Agent for Type 2 Diabetes Mellitus

Dubourg, J., et al. Eur J Clin Pharmacol — 2020

In Vitro Investigation, Pharmacokinetics, and Disposition of Imeglimin, a Novel Oral Antidiabetic Drug, in Preclinical Species and Humans

Clemence, C., et al. Drug Metab Dispos — 2020

Lack of Drug-Drug Interaction Between Cimetidine, a Renal Transporter Inhibitor, and Imeglimin, a Novel Oral Antidiabetic Drug, in Healthy Volunteers

Chevalier, C., et al. Eur J Drug Metab Pharmacokinet — 2020

Pharmacokinetics of Imeglimin in Subjects with Moderate Hepatic Impairment

Chevalier, C., et al. Clin Pharmacokinet — 2020

Imeglimin Protects Ins-1 Cells And Human Islets Against High Glucose- And High Fructose-induced Cell Death By Inhibiting The Mitochondrial PTP Opening

Sandrine Lablanche et al. — June 2018, ADA (American Diabetes Association), Orlando, USA

Imeglimin monotherapy in Japanese patients with type 2 diabetes: results from a randomised, 24-week, double-blind, placebo-controlled, phase IIb trial

J. Dubourg — September 2017, EASD (European Association for the Study of Diabetes), Lisbon, Portugal

Short- and long-term imeglimin treatment reduces metabolic syndrome-related diabetic cardiomyopathy

Marianne Lachaux et al. — August 2017, EASD (European Association for the Study of Diabetes), Barcelona, Spain

Imeglimin Opposes Development of Metabolic Syndrome Related Diabetic Cardiomyopathy

Marianne Lachaux et al. — June 2017, ADA (American Diabetes Association), San Diego, USA

Imeglimin Preserves β-cell Function and Mass in Male Zucker Diabetic Fatty Rats World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease

Sophie Hallakou-Bozec et al. — December 2016, WCIRDC (World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease), Los Angeles, California, USA

Imeglimin Improves Vascular Dysfunction in Type 2 Diabetes Animal Models EASD

Fouqueray P et al. — September 2016, EASD (European Association for the Study of Diabetes), Munich, Germany

Imeglimin Improves Insulin Sensitivity in an Adult STZ Rat Model ADA

Sophie Hallakou-Bozec et al. — June 2016, ADA (American Diabetes Association), New Orleans, USA

Imeglimin Increases Insulin Secretion in Response to Glucose as a Unique Mechanism of Action Depending on NAD Synthesis ADA

Sophie Hallakou-Bozec et al. — June 2016, ADA (American Diabetes Association), New Orleans, USA

Imeglimin Lowers Glucose Primarily by Amplifying Glucose-stimulated Insulin Secretion in High-fat-fed Rodents

Perry, R.J., et al. Am J Physiol Endocrinol Metab — 2016

Imeglimin Prevents Human Endothelial Cell Death by Inhibiting Mitochondrial Permeability Transition Without Inhibiting Mitochondrial Respiration

Detaille, D., et al. Cell Death Discov — 2016

Imeglimin, a New Oral Anti-Hyperglycemic Agent Controls Fasting and Post-Prandial Glucose through an Improvement in both Insulin Secretion and Insulin Sensitivity WCIRDC

Fouqueray P et al. — November 2015, WCIRDC (World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease), Los Angeles, USA

Dose Ranging-Study to Determine the Optimum Dose for Imeglimin, a Novel Treatment for Type 2 Diabetes.

Fouqueray P et al. — June 2015, ADA (American Diabetes Association), Boston, USA

Imeglimin Normalizes Glucose Tolerance and Insulin Sensitivity and Improves Mitochondrial Function in Liver of a High-fat, High-sucrose Diet Mice Model

Vial, G., et al. Diabetes — 2015

Imeglimin Increases Glucose-dependent Insulin Secretion and Improves Beta-cell Function in Patients with Type 2 Diabetes

Pacini, G., et al. Diabetes Obes Metab — 2015

Imeglimin decreases hepatic glucose production through a unique mitochondrial mechanism of action.

Vial G et al. — June 2014, ADA (American Diabetes Association), San Francisco, USA

The Efficacy and Safety of Imeglimin as Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled with Sitagliptin Monotherapy

Fouqueray, P., et al. Diabetes Care — 2014

Imeglimin: A new antidiabetic agent that provides added benefit to DPP-4 inhibitor therapy.

Fouqueray P et al. — June 2013, ADA (American Diabetes Association), Chicago, USA

The Efficacy and Safety of Imeglimin as Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy

Fouqueray, P., et al. Diabetes Care — 2013

The efficacy and safety of imeglimin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy

Fouqueray P et al. — June 2012, ADA (American Diabetes Association), Philadelphia, USA

公表論文・ポスター発表資料

PXL770 - AMP Kinase Activators

PXL065 - Deuterium-Stabilized Thiazolidinediones

Imeglimin - Type 2 Diabetes