TrkA is the high affinity receptor for nerve growth factor (NGF). NGF is a small protein and is essential for the life of nerve cells, i.e. the neurons. However, under pathological conditions, NGF acts as a major mediator of pain, and the interaction of NGF with TrkA is a key event in this respect.
Monoclonal antibodies against NGF represent one of the rare clinical breakthroughs for the treatment of chronic pain (e.g. Pfizer’s tanezumab), including osteoarthritis pain. Unfortunately, development of the class has been delayed due to findings of severe joint toxicity.
Monoclonal antibodies against TrkA may have an advantage over anti-NGF antibodies, in that they do not deplete NGF pools and are anticipated to have a better safety profile.
Rottapharm Biotech is developing fully human monoclonal antibodies (mAb) that specifically recognize human TrkA with nanomolar affinity. The lead molecule CRB0089 has a potent, long-lasting analgesic activity in animal models of chronic, inflammatory, and neuropathic pain.
Lead optimization is ongoing, and candidate selection is expected by the end of 2019.