Pretzel Therapeutics announced that it will present new preclinical data demonstrating that targeting mitochondrial RNA polymerase (POLRMT) produced significant weight loss and improved metabolic markers in diet-induced obese mouse models. According to the company, these findings were featured at ObesityWeek 2025 in Atlanta and underscore POLRMT’s potential as a novel therapeutic mechanism for metabolic disease.
The company said that the data involve a liver-directed antisense oligonucleotide (ASO) that knocked down POLRMT in mice, resulting in increased energy expenditure, enhanced glucose homeostasis, reduced fat mass while preserving lean mass, and improved body composition. Pretzel claims that the study illustrates how inhibiting mitochondrial transcription and oxidative phosphorylation biogenesis can modulate energy balance and combat obesity and metabolic dysfunction.
According to Pretzel Therapeutics, POLRMT is the lead program in its “energetics modulation” franchise and is currently in late preclinical development. The company said that the initiative complements its “bioenergetics restoration” pipeline and positions Pretzel to advance therapies for metabolic conditions and other age-related diseases by harnessing mitochondrial biology.
The company claims that this research reinforces its platform strategy of targeting cellular energetics across a broad range of indications, including rare, neurological, muscle and metabolic disorders. Pretzel said that additional analyses from the presentation will be made available on its website following the conference.
