First in Class Antibody Drug Conjugate for Targeting CD56 Positive Brain Tumors
CURB906 is our fully humanized CD56 monoclonal antibody carrying a cytotoxic drug conjugate directly to the tumor site to kill the tumor by inhibiting tumor growth and migration of the tumor. The technology was originally developed at the National Cancer Institute (NCI) at the National Institutes of Health (NIH) in collaboration with Children’s Hospital of Philadelphia (CHOP).
Monoclonal antibodies by their very nature are incredibly target specific. With CURB906, we are targeting CD56 positive brain tumors. Among the functions CD56 are involved with (also known as a neural cell adhesion molecule or NCAM) is cell migration and growth. We are targeting these cells on the tumors to stop both of those functions. CD56 is overexpressed on brain tumors, particularly early-stage tumors. The antibody will carry an extremely potent anticancer drug conjugate such as PBD (pyrollobenzodiazapine) or similar structural analogs. PBDs can be 100 to even 1,000 times more potent than chemotherapy drugs and have been shown to have broad-spectrum anti-tumor activity in vivo. These novel drugs exert their activity by binding in the minor groove of DNA and linking the two DNA strands together in a way that cells find difficult to recognize and repair.
This increased potency, however, comes with an increased urgency to make sure that the drug is only delivered to the target. That is why a monoclonal antibody is an ideal vehicle to deliver this “payload.”
Historically, it has been difficult to get monoclonal antibodies across the Blood Brain Barrier (BBB) and so to ensure that we are delivering enough drug to the tumor, as well as to limit the delivery of the drug as much as possible to the tumor site, we are administering the drug through surgical intervention directly to the remaining tumor during surgery to remove whatever part of the tumor can be removed safely. This allows the drug to attack whatever partial tumor material remains.
IMT504 is a novel immune therapy to treat rabies. Currently, there is no effective therapy for rabies encephalitis. Vaccines are available only for pre-exposure and immediate post-exposure prophylaxis. Once signs of infection develop, however, there is no effective treatment and, uniquely among infectious diseases, it has a case fatality rate of almost 100%. Current vaccines are effective at protecting against this outcome provided that the vaccination is given before or shortly after exposure to a biting incident.
IMT504 is an oligodeoxynucleotide (ODN). ODNs are synthetic molecules that stimulate different kinds of cells of the immune system of animals and humans and have been studied as vaccine adjuvants, as well as cancer and infectious disease immunotherapy. ODNs cause B cells and plasmacytoid dendritic cells to activate, proliferate, secrete immunoglobulin, and express co-stimulatory molecules.
IMT504 has been shown to be effective in creating survival in a gold standard animal model meant to simulate treatment LATER than the window where current vaccines are known to be effective. In early human volunteer safety testing, IMT504 was highly immunogenic and well-tolerated in all volunteers.