Chemotherapy-induced peripheral neuropathy (CIPN) is a constellation of symptoms that appear in patients receiving chemotherapy to treat cancer. The incidence can be as high as 95% depending on the type and dose of chemotherapy agent. These agents include taxanes (e.g. paclitaxel), platinum compounds (e.g. oxaliplatin), bortezomib, vinka alkaloids (e.g. vincristine), thalidomide, lenalidomide, epothilones, antibody drug conjugates (e.g. MMAE), and others. Typically CIPN presents as a distal (foot and hand) sensory neuropathy with patients complaining of numbness, tingling, and burning pain. CIPN usually begins weeks to months after initiation of chemotherapy and usually lasts for months to years following cessation.

 

An optimal treatment to prevent CIPN would be administered before chemotherapy is started. It would protect neurons from CIPN damage without affecting the efficacy of the chemotherapeutic agents or causing systemic side effects. The most efficient manner to achieve this goal would be to target a treatment directly to sensory neurons. PeriphaGen's NET platform allows for transduction of sensory neurons in a safe and efficient manner following administration of the vector to the skin.

 

PGN-503 can prevent the development of neuropathy in animal models of oxaliplatin, paclitaxel, bortezomib, and cisplatin CIPN. Neurotrophic factors can prevent the development of peripheral neuropathy but systemic delivery is associated with dose limiting toxicities in humans. PeriphaGen's NET drug, PGN-503, expresses Neurotrophin-3 and prevents the development of CIPN in animals treated with paclitaxel, oxaliplatin, cisplatin, and bortezomib. It can reverse (i.e. treat) an established paclitaxel neuropathy. PeriphaGen is currently moving towards clinical trials to prove the safety and efficacy of PGN-503 to prevent or treat paclitaxel, oxaliplatin, and bortezomib induced peripheral neuropathies.