TLC-1180 / OrsoBio - LARVOL DELTA

The Protonophore TLC-1180 Drives Weight Loss, Alone and Combined With Semaglutide, in Obese Primates (OBESITY WEEK 2025) - "In spontaneously obese NHPs, TLC-1180 monotherapy caused comparable or superior body weight and fat mass loss to SEMA monotherapy. A combination of TLC-1180 with SEMA further enhanced body weight and fat mass loss and was superior to SEMA monotherapy. These data highlight the potential for TLC-1180 as monotherapy or in combination with incretins in the treatment of obesity and associated metabolic disorders."

Genetic Disorders • Metabolic Disorders • Obesity

TLC-1180, a Protonophore, With Semaglutide Enhances Weight Loss and Preserves Lean Mass in DIO Mice (OBESITY WEEK 2025) - "In DIO mice, TLC-1180 monotherapy is lean mass neutral and caused body weight and fat mass loss similar to high-dose SEMA. These benefits were amplified in combination with a low dose of SEMA. These data highlight the potential benefits of TLC-1180 as monotherapy or in combination with low-dose incretins in the treatment of obesity."

Preclinical • Genetic Disorders • Obesity

Oral-013: TLC-1180, a Protonophore, with Semaglutide Enhances Weight Loss and Preserves Lean Mass in DIO Mice (Businesswire) - "This preclinical study evaluated the effects of TLC-1180 alone and in combination with low-dose semaglutide, compared with high-dose semaglutide, in DIO mice. As monotherapy, TLC-1180 produced body weight and fat mass loss comparable to high-dose semaglutide. In combination with low-dose semaglutide, TLC-1180 achieved greater weight and fat mass reduction with comparable-to-superior metabolic benefits without exacerbating incretin-induced lean mass loss. These findings support a clinical strategy combining a protonophore with a low-dose incretin to minimize adverse effects and improve long-term adherence without compromising efficacy in individuals with obesity."

Preclinical • Obesity

Poster-254: The Protonophore TLC-1180 Drives Weight Loss, Alone and Combined with Semaglutide, in Obese Primates (Businesswire) - "This preclinical study evaluated the effects of TLC-1180, alone and in combination with semaglutide, versus semaglutide monotherapy in spontaneously obese non-human primates. As monotherapy, TLC-1180 produced dose-dependent reductions in body weight, fat mass, and plasma insulin while preserving lean mass. After seven weeks, low-dose TLC-1180 and semaglutide achieved similar vehicle-adjusted weight loss (11% and 14%, respectively), while high-dose TLC-1180 achieved greater weight loss (20%). The combination of TLC-1180 and semaglutide produced the most pronounced effects—27% weight loss and a 67% reduction in fat mass—without affecting food intake or lean mass. These results support the evaluation of TLC-1180, alone and with incretins, for the treatment of obesity and related metabolic disorders."

Preclinical • Obesity

De Novo or Sequential Combination of the Mitochondrial Protonophore TLC-1180 with Semaglutide Improves Weight Loss and Preserves Lean Mass in Dio Mice (ADA 2025) - "In DIO mice, '1180 caused BW and FM loss while preserving LM. These benefits were amplified in combo with SEMA and maintained post SEMA D/C. These data highlight the potential of '1180 as mono and in combo with incretins in obesity and associated metabolic disorders."

Preclinical • Metabolic Disorders • Obesity

Novel Combination of a Mitochondrial Protonophore (MP) and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice (ADA 2025) - "Introduction and Objective: TLC-1180 , a novel MP, and TLC-3595, an ACC2-selective inhibitor, enhance fatty acid oxidation via complementary mechanisms and are in development for obesity-associated disorders. In DIO mice, a novel combo of a MP and an ACC2 inhibitor caused comparable weight loss to an incretin but preserved lean mass. In sum, these data support the evaluation of combinations of these agents in people living with obesity and associated metabolic disorders."

Preclinical • Metabolic Disorders • Obesity • ACACB

De Novo or Sequential Combination of the Mitochondrial Protonophore TLC-1180 With Semaglutide Improves Weight Loss and Preserves Lean Mass in DIO Mice (Businesswire) - "OrsoBio...announced new preclinical data being presented at the 85th Scientific Sessions of the American Diabetes Association (ADA)....This preclinical study evaluated the effects of TLC-1180 alone, in combination with semaglutide, and as a maintenance treatment following semaglutide discontinuation in DIO mice. As monotherapy, TLC-1180 demonstrated body weight and fat mass loss and preserved lean mass. Body weight and fat mass loss were amplified, and lean mass was preserved with TLC-1180 in combination with semaglutide. These benefits persisted when TLC-1180 was used as a maintenance treatment after semaglutide discontinuation."

Preclinical • Obesity

Novel Combination of a Mitochondrial Protonophore and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice (Businesswire) - "OrsoBio...announced new preclinical data being presented at the 85th Scientific Sessions of the American Diabetes Association (ADA)....This preclinical study evaluated the effects of the mitochondrial protonophore, TLC-1180, and the ACC2 inhibitor, TLC-3595—as monotherapy and in combination—and semaglutide in DIO mice. TLC-3595 dose dependently reduced body weight, fat mass, and liver biochemistry while preserving lean mass in DIO mice. A combination of TLC-3595 with TLC-1180 had similar weight loss efficacy to semaglutide, but preserved lean mass."

Preclinical • Obesity