Science

Levicept is developing LEVI-04 (p75NTR-Fc), a novel biological agent for the treatment of chronic pain. It modulates the clinically-validated neurotrophin pathway and is designed to restore neurotrophin homeostasis and thereby lead to profound, yet safe, analgesia.

Clinical trials with antibodies to nerve growth factor (NGF) have demonstrated the efficacy of anti-NGF antibodies (eg tanezumab, fulranumab) in chronic pain conditions such as osteoarthritis, back pain and cancer pain. However, anti-NGF treatment is associated with rapid progression of osteoarthritis, leading to early joint replacement for some patients. In pre-clinical models of osteoarthritis, administration of p75NTR-Fc provides analgesia equivalent to that achieved with anti-NGF antibody treatment, but without rapid progression of osteoarthritis.

A Phase I clinical trial of LEVI-04 in osteoarthritis patients confirmed favourable safety, tolerability and pharmacokinetic profile. Analysis of biomarkers indicated target engagement and provided early supporting evidence of efficacy / proof-of-concept. A 500+ patient Phase II trial is ongoing.

p75NTR-Fc is a chimeric fusion protein, combining the Fc fragment of a human immunoglobulin G1 with the neurotrophin receptor (NTR). p75NTR-Fc treatment delivers neurotrophin homeostasis by providing stable binding proteins for the excess neurotrophins present in chronic pain states. It operates across multiple pathways in the neurotrophin system and is designed to supplement the existing endogenous system and return it to normal functioning. Importantly, unlike anti-NGF antibodies which ablate NGF signalling as they bind irreversibly to NGF, p75NTR-Fc provides analgesia while maintaining the neurotrophin function required for cartilage and bone repair.

LEVI-04 (p75NTR-Fc) is a first-in-class proprietary fusion protein. It is being developed as an once a month injectable for the treatment of osteoarthritis and chronic pain.