CRB0089 and other compounds in this series are novel anti-TrkA therapeutic antibodies characterized by potent analgesic activity.
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, 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’s biotherapeutics against TrkA are fully human recombinant antibodies that specifically recognize the extracellular domain of human TrkA and bind it with high (nanomolar) affinity. In vitro studies have shown that they block in a dose-dependent manner the biological effects induced by NGF binding to TrkA.
The lead molecule CRB0089 has a potent, long-lasting analgesic activity in animal models of chronic, inflammatory, and neuropathic pain. Subcutaneous administration of CRB0089 inhibited the hyperalgesia (exaggerated pain perception) and pain responses induced by a variety of painful stimuli.
Candidate selection for preclinical development is ongoing.