What question did this study set out to answer?

The study aims to evaluate the efficacy of Myo-004 in inducing body weight loss and its metabolic effects in DIO mice.

June 7, 2026

1802-P: Myo-004 Induces Body-Weight Loss in DIO at Thermoneutrality by Switching Metabolism from Fat to Carbohydrate Oxidation

Key Points

The study aims to evaluate the efficacy of Myo-004 in inducing body weight loss and its metabolic effects in DIO mice.
Male C57BL/6J mice fed high-fat diet or standard chow for 15 weeks with Myo-004 dosed at 1 and 5 mg/kg;
Comparative interventions included tirzepatide and bimagrumab with assessments on body weight and metabolic parameters.
Metabolic cages, body composition (MRI), fasting glucose, insulin, and grip strength were measured over 8 weeks.
Myo-004 at 5 mg/kg resulted in significant body weight loss while maintaining calorie intake compared to tirzepatide.
Myo-004 demonstrated durable fat mass reduction and preserved lean mass, contrasted with GLP-1RA effects.
Increased RER and carbohydrate oxidation were noted, indicating a shift in metabolism without affecting overall activity.

Abstract

Introduction and Objective: GLP-1RA drugs have revolutionised the treatment of obesity and provides novel therapeutic options. However, real world data highlight limitations in terms of long-term efficacy, lean mass preservation and tolerability. Our mitochondrial-targeted small molecules provide an alternative mode-of-action to modulate metabolism to combat obesity. Methods: Male C57BL/6J mice fed high-fat diet (60%) or standard chow from week 6 of age for 15 weeks were dosed with Myo-004 (1 and 5 mg/kg; s.c. TIW), tirzepatide (5 nmol/kg, s.c. QD), bimagrumab (20 mg/kg, s.c, QW) or combinations for 8 weeks (n=10). Body weight, food intake, fasting glucose, insulin, OGTT, metabolic cages, grip strength and body composition (MRI) were assessed. Blood/plasma were harvested for biochemical and histological evaluation. Results: At thermoneutrality, Myo-004 (5 mg/kg) was well tolerated and demonstrated significant body weight loss surpassing tirzepatide without affecting calorie intake. During long-term dosing in DIO models, GLP-1RA weight loss is reversed: Myo-004, on the contrary, drove continuous linear BWL over 8 weeks. Myo-004 significantly decreased fat mass more durably and extensively than tirzepatide while preserving lean mass. Myo-004 increased RER, decreased fat oxidation and increased carbohydrate oxidation without affecting activity, rearing or energy expenditure. Conclusion: Altogether, Myo-004 demonstrates potent anti-obesogenic properties that are long lasting in the DIO model at thermoneutrality. Bodyweight loss is associated with strong reduction in fat while preserving lean mass as well as grip-strength suggesting muscle function preservation. Improvement in metabolic capacity (increased RER) and a switch between fat and carbohydrates oxidation support a differentiated mode-of-action from incretins or uncouplers thus providing alternative solutions for individuals living with obesity or for maintenance therapies after incretins therapy cessation. Disclosure X. Jacq: Employee; Current; MitoRx Therapeutics. R. Torregrossa: None. N. Law: Employee; Current; MitoRxTherapeutics Ltd. R. Cousins: Employee; Current; MitoRx Therapeutics Limited. J. Rees: Employee; Current; MitoRx Therapeutics Ltd.

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