Science & Pipeline
Pretzel is focused on discovering and advancing novel medicines that address dysregulated cellular energetics at their source
Leveraging advanced mitochondrial science, we aim to restore mitochondrial function, improve cellular energetics and modify disease progression in conditions driven by low mitochondrial DNA (mtDNA). By targeting the root cause of mitochondrial depletion which leads to multi-systemic dysfunction, we have the potential to meaningfully improve survival, functional outcomes and quality of life for patients across many high unmet need indications.
Pretzel is building a deep, first-in-class pipeline of novel medicines designed to target fundamental drivers of disease biology across neurodegenerative and rare diseases associated with low mtDNA levels.
*obesity/metabolic programs recently licensed to obesity-focused stealth newco
PX578
PX578 is a first-in-class, CNS penetrant small molecule activator of the mitochondrial polymerase POLG designed to increase mtDNA levels, enhance mitochondrial function and improve quality of life by halting or reversing disease progression across mitochondrial disorders, including POLG-mediated primary mitochondrial disease (POLG disease), a rare and often devastating condition for which no approved disease-modifying therapies currently exist. Preclinical studies across multiple in vitro and in vivo models, as well as a recently completed Phase 1 healthy volunteers study, support the disease-modifying potential of PX578 and its advancement into Phase 2 clinical evaluation in adult patients with POLG disease planned for late 2026.
SAMHD1
SAMHD1, the second target in our energetics restoration franchise, is a key driver of mtDNA levels and represents another promising avenue for increasing mtDNA levels. This program is in preclinical development.