The dual opioid-NPFFR pharmacology of KGFF09 within a single molecule gathers the beneficial effects of G protein-biased MOR agonism on MOR-related side effects (respiratory depression, reward and sedation/locomotor activity) and those of NPFFRs antagonism on chronic side effects (opioid-induced hyperalgesia, tolerance and withdrawal syndrome). Here, OPRM1 is linked to respiratory depression.