GT103 Program

Grid Therapeutics has the exclusive, global rights to a novel antibody (GT103) against a unique target for the treatment of lung cancer with applications in multiple cancer types. The discovery was made by Dr. Patz and his laboratory at Duke University Medical Center, who used an innovative strategy that explored the host response in a distinct group of lung cancer patients with early-stage disease who never developed metastasis. They discovered that many of these patients had a high affinity antibody that inhibits an essential tumor cell-protective protein complement factor H (CFH), thus permitting tumor cell death through activation of the complement cascade, with resultant modulation of the adaptive immune response to potentially create a long-term durable response. This antibody causes no adverse effects in the lung cancer patients who possess it. Dr. Patz recognized the therapeutic value of this antibody, not only in lung cancer, but in other types of cancer, because many solid tumor types use the same protective mechanism to prevent destruction by complement.

To generate a therapeutic antibody, Grid used a unique strategy in order to clone and express the genes that code for the anti-CFH antibody. Specific antibody-producing B cells were isolated from the peripheral blood of these exceptional patients, the immunoglobulin genes were cloned and expressed, and high affinity recombinant human monoclonal antibodies were produced, including GT103. GT103 binds a conformationally distinct epitope within a specific crucial functional domain on tumor cell bound CFH. Upon binding to CFH, the antibody triggers complement dependent cytotoxicity, resulting in tumor cell death. In mouse models, GT103 inhibits tumor growth and modulates the adaptive immune response, dramatically reducing the number of immune suppressive T regulatory cells and myeloid-derived suppressor cells in the tumor. The adaptive immunity triggered by GT103 is an area of active investigation.

Grid Therapeutics was formed to translate this discovery into a novel therapeutic product and treatment approach. GT103, a fully human monoclonal antibody, has been manufactured for a Phase I clinical trial in advanced stage cancer patients. The FDA has issued an IND to Grid Therapeutics to proceed with the trial.

Following a first-in-man Phase I trial, an extensive clinical development plan will be executed to test the antibody in multiple cancer types, potentially with combination therapy. The drug can be used in a substantially larger patient population than current therapies. Key differentiators for this asset are the facts that this completely human derived antibody was discovered in “exceptional outcomes” patients, recognizes a unique tumor specific epitope, and modulates the adaptive immune response to potentially induce long-term immunity.