AptamiR Therapeutics has created a revolutionary approach to cure human obesity and related cardio-metabolic disorders like insulin resistance and fatty liver by converting fat-storing adipocytes into fat-burning adipocytes.

AptamiR Therapeutics Summary

Structure: AptamiR is a US modular Biotechnology Company currently completing the pre-clinical development phase of its drug candidates

Mission: Treat fat accumulation, inflammation and necrosis to cure related cardiometabolic disorders (dyslipidemia, diabetes and metabolic dysfunction-associated fatty liver disease (MAFLD)), without altering brain functions, but improving patients quality of life

Strategy: Transform fat-storing cells (white adipocytes) into fat-burning cells (“browning effect”) to increase lipid oxidation, mitochondrial activity and energy expenditure

Accomplishment to date: Proofs of efficacy for our first generation of Oligonucleotide Therapeutics (ONTs) targeting microRNAs were achieved in vitro in primary cultures of human adipocytes and in vivo in animal models of obesity and fatty liver disease

Goal for the next 24 months: Complete the pre-IND and IND phases for our second generation of targeting miR-22-3p Antagomirs to treat the Metabolic Pandemics obesity, diabetes and fatty liver disease

Gap to achieve this goal: Secure the first tranche ($5M) of Series B financing

Major milestone: Initiate within 2 years the clinical studies for the lead miR-22-3p antagomir drug candidate of the second generation

End goal:

• Help patients live longer, productive and healthier lives while reducing healthcare costs
• Develop safe, effective, and convenient treatments for obesity, diabetes, and MAFLD in companion dogs and cats

News

Oral presentation at the 2021 TIDES USA (Oligonucleotide & Peptide Therapeutics) Conference in Boston, MA:

Title: Oligonucleotide Therapeutics with a Peptide Nucleic Acid Backbone to Treat Metabolic Pandemics

AptamiR Therapeutics is developing its second generation of miRNA antagomirs with a Peptide Nucleic Acid backbone which are conjugated to a fatty acid or a short peptide for targeted and preferential cytoplasmic delivery to adipocytes through the trans-membrane transporter Fatty Acid Translocase (FAT). The effective dose of these drug candidates should be much lower with a greatly improved safety and PK/PD profile, especially their mean residence time inside the targeted cells.

Slides:

Article recently published in BMJ Open Diab Res Care:

BMJ Open Diab Res Care 2020;8:e001478. doi:10.1136/bmjdrc-2020-001478

Title: Metabolic and Energetic Benefits of microRNA-22 Inhibition

Abstract

Introduction: We previously demonstrated in primary cultures of human subcutaneous adipocytes and in a mouse model of diet- induced obesity that specific microRNA-22- 3p antagomirs produce a significant reduction of fat mass and an improvement of several metabolic parameters. These effects are related to the activation of target genes such as KDM3A, KDM6B, PPARA, PPARGC1B and SIRT1 involved in lipid catabolism, thermogenesis, insulin sensitivity and glucose homeostasis.

Research design and methods: We now report a dedicated study exploring over the course of 3 months the metabolic and energetic effects of subcutaneous administration of our first miR-22- 3p antagomir drug candidate (APT-110) in adult C57BL/6 male mice. Body composition, various blood parameters and energy expenditure were measured at several time-points between week 12 and week 27 of age.

Results: Weekly subcutaneous injections of APT-110 for 12 weeks produced a sustained increase of energy expenditure as early as day 11 of treatment, a significant fat mass reduction, but no change of appetite nor physical activity. Insulin sensitivity as well as circulating glucose, cholesterol and leptin were improved. There was a dramatic reduction of liver steatosis after 3 months of active treatment. RNA sequencing revealed an activation of lipid metabolism pathways in a tissue- specific manner.

Conclusions: These original findings suggest that microRNA-22- 3p inhibition could lead to a potent treatment of fat accumulation, insulin resistance, and related complex metabolic disorders such as obesity, type 2 diabetes mellitus and non- alcoholic fatty liver disease.