To evaluate the efficacy and safety of KHN702 in the treatment of pain. 

Pain is a serious public health issue, which affects more than 20% of the global population. Analgesics as the mainstay of pain treatment, have a huge and unmet medical need. Current treatment options for pain management are often limited, carry a spectrum of adverse effects and are potentially addictive, highlighting the urgent need for improved pain therapies. Nav1.8 is a voltage-gated sodium channel predominately expressed in the peripheral sensory neurons, which plays a crucial role in pain transmission, suggesting that its inhibition might treat pain while avoiding central adverse effects. KHN702 is a novel, non-opioid, highly selective Nav1.8 inhibitor in development for treatment of pain. 

The mechanism of action study was performed in vitro using electrophysiology method in cells expressing hNav1.8. The analgesic effects were assessed in plantar incision pain model, CFA-induced inflammatory pain model and SNL neuropathic pain model. Pharmacokinetic profile were evaluated in rat and monkey. Safety assessments included in vitro secondary pharmacology and genetic toxicity studies, nonclinical repeat-dose toxicity in rats and canine. 

KHN702 demonstrated good in-vitro potency and selectivity. When compared to VX-548 in head-to-head comparative studies, KHN702 showed compelling advantages including superior pharmacokinetic profiles in rat and monkey, faster on set of action and better analgesic effects in acute and chronic pain models as well as higher safety windows. 

Nav1.8 represents a novel and non-addictive target for the treatment of pain. KHN702 demonstrated favorable efficacy and safety profile which is currently undergoing phase I study (CTR20252159). The preliminary results show that KHN702 is safe and well-tolerated, no serious or severe AEs were observed. These results support continued evaluation of KHN702 as a novel non-opioid treatment for pain.