adiponectin analogue (ALY688) / Allysta Pharma - LARVOL DELTA

Development of a non-invasive bioassay for adiponectin target engagement in mice. (PubMed, iScience) - "We also confirmed a functional outcome of ALY688 action in mice as our study also demonstrated the anti-inflammatory effect of ALY688 in a sublethal LPS mouse model. In summary, a newly identified gene cluster signature is suitable for assessing the pharmacodynamic action of adiponectin or its mimetics in blood samples."

Journal • Preclinical • Inflammation • Metabolic Disorders

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from gamma-delta T cells (SHC 2024) - No abstract available.

Psoriasis

A novel blood-based bioassay to monitor adiponectin signaling. (PubMed, Int Immunopharmacol) - "Specifically, we tested effects of the small 10-amino acid peptide adiponectin receptor agonist, ALY688, in a sublethal LPS endotoxemia model in mice...Together, these results indicate we can detect adiponectin action on immune cells in vivo by assessing adiponectin signaling pathway for AMPK and p38-MAPK, as well as pro-inflammatory cytokine levels. This new approach provides a blood-based bioassay for screening adiponectin action."

Journal • Inflammation • Metabolic Disorders • AMPK • TGFB1

Cardioprotection by the adiponectin receptor agonist ALY688 in a preclinical mouse model of heart failure with reduced ejection fraction (HFrEF). (PubMed, Biomed Pharmacother) - "These results indicate that the adiponectin mimetic peptide ALY688 reduced PO-induced fibrosis, hypertrophy, inflammation and metabolic dysfunction and represents a promising therapeutic approach for treating HFrEF in a clinical setting."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • Metabolic Disorders • CCL3 • CCL4 • IL13 • IL17A • IL1B • IL5 • IL6 • POSTN • TIMP1 • TLR4

Identification of Mechanisms via Which the Adiponectin Receptor Agonist ALY688 Confers Cardioprotective Effects in Preclinical Models of Heart Failure (AHA 2023) - "In the pressure overload model, ALY688 increased myocardial fatty acid oxidation, with increased mobilization of cardiac triacylglycerols and a decrease in sphingomyelin, fatty acids and lysophospholipids, measured by targeted metabolomics. In conclusion, ALY688 had cardioprotective effects in two well established preclinical animal models of heart failure, suggesting outstanding promise for translation to a clinical approach."

Late-breaking abstract • Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Metabolic Disorders • Reperfusion Injury • AMPK

The Adiponectin Receptor Agonist, ALY688: A Promising Therapeutic for Fibrosis in the Dystrophic Muscle. (PubMed, Cells) - "ALY688's protective and beneficial properties were mainly mediated by the AMPK-PGC-1α axis, which led to suppression of NF-κβ and TGF-β. Our results demonstrate that an ApN mimic may be a promising and effective therapeutic prospect for a better management of DMD."

Journal • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy • Myositis • AMPK • TGFB1

The Adiponectin Receptor Agonist ALY688 Prevents Pressure Overload-induced Cardiac Dysfunction And Adverse Cardiac Remodeling (BCVS 2023) - "Abstract is embargoed at this time."

Intervention With The Adiponectin Mimetic Peptide ALY688 Protects Against Cardiac Dysfunction Induced By Ischemia Reperfusion Injury (BCVS 2023) - "Abstract is embargoed at this time."

Cardiovascular • Reperfusion Injury

Memory impairment in the D2.mdx mouse model of Duchenne muscular dystrophy is prevented by the adiponectin receptor agonist ALY688. (PubMed, Exp Physiol) - "Each of these measures was partly or fully preserved after treatment with ALY688. Collectively, these results indicate that adiponectin receptor agonism improves recognition memory in young D2.mdx mice."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • IL6

Potent Anti-inflammatory Effects of the Adiponectin Receptor Agonist, ALY688 (P855) (IMMUNOLOGY 2023) - "These results were confirmed in human peripheral blood mononuclear cells (PBMCs), where ALY688 treatment led to a robust increase in phospho-AMPK and phospho-P38. Altogether, these results show that the adiponectin agonist, ALY688, has strong anti-inflammatory effects by triggering AMPK and P38 activation in vivo and in vitro."

Addiction (Opioid and Alcohol) • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hepatology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Obesity • Type 2 Diabetes Mellitus • IFNB1 • IL12A • IL1B • TGFB1 • TNFA

A Phase 1/2a Study of ALY688 Ophthalmic Solution in Dry Eye Subjects (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • P1/2 data • Dry Eye Disease • Ocular Inflammation • Ophthalmology

OASIS-1: ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2b | N=922 | Completed | Sponsor: Allysta Pharmaceutical | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

OASIS-1: ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2b | N=922 | Active, not recruiting | Sponsor: Allysta Pharmaceutical | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2022 ➔ Feb 2023 | Trial primary completion date: Mar 2022 ➔ Feb 2023

Enrollment closed • Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

ALY688 elicits adiponectin-mimetic signaling and improves insulin action in skeletal muscle cells. (PubMed, Am J Physiol Cell Physiol) - "Importantly, we observed that ALY688 administration to high-fat high sucrose fed mice also improve glucose handling, validating its efficacy in vivo. In summary, these data indicate that ALY688 activates adiponectin signaling pathways in skeletal muscle, leading to improved insulin sensitivity and beneficial metabolic effects."

Journal • Diabetes • Immunology • AKT1 • AMPK

OASIS-1: ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2b; N=900; Recruiting; Sponsor: Allysta Pharmaceutical; Phase classification: P2a ➔ P2b

Clinical • Phase classification • Dry Eye Disease • Ophthalmology

OASIS-1: Phase 2a/3 Safety and Efficacy of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2a; N=900; Recruiting; Sponsor: Allysta Pharmaceutical

Clinical • New P2a trial • Dry Eye Disease • Ophthalmology

Phase 1/2a Safety and Efficacy of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (clinicaltrials.gov) - P1/2; N=138; Completed; Sponsor: Allysta Pharmaceutical; Active, not recruiting ➔ Completed

Clinical • Trial completion • Dry Eye Disease • Ocular Infections • Ophthalmology

Effects of the adiponectin mimetic compound ALY688 on glucose and fat metabolism in visceral and subcutaneous rat adipocytes. (PubMed, Adipocyte) - "Adiponectin receptor 2 (AdipoR2) mRNA was the prevalent isoform expressed in all adipocytes, and Epid adipocytes displayed significantly higher AdipoR2 mRNA expression than Sc Ing adipocytes. In conclusion, ALY688 can regulate adiposity and affect glycaemic control by altering substrate portioning in the WAT in a fat depot-specific manner."

Journal • Preclinical • Atherosclerosis • Dyslipidemia • Metabolic Disorders • Obesity • AMPK

Phase 1/2a Safety and Efficacy of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (clinicaltrials.gov) - P1/2; N=138; Active, not recruiting; Sponsor: Allysta Pharmaceutical; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Dry Eye Disease • Ophthalmology

Newly added product (clinicaltrials.gov) - P2, Dry Eye Disease, Ophthalmology

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