Overview

GT Biopharma, Inc. (NASDAQ: GTBP) is a clinical stage immuno-oncology company focused on innovative therapies based on the Company's proprietary NK cell engager (TriKE®) technology.

TriKE® therapeutic agents are targeted immunotherapeutic agents that have been modified from a bispecific antibody platform. TriKE agents are camelid nanobody-based immune cell engagers that are designed to bridge natural killer (NK) cells to cancer cells for the selective targeting and killing of cancer cells. TriKE therapeutic agents that are currently under development consist of three functional moieties: a camelid nanobody that binds the CD16 receptor on NK cells, a single chain variable fragment (scFv) that recognizes a marker expressed on the tumor cell, and a human interleukin (IL)-15 cross-linker. The IL-15 component of TriKE provides a self-sustaining signal that activates NK cells and enhances their ability to kill tumor cells.

TriKE® therapeutic agents, due in part to their IL-15 component, not only activate NK cells, but also display more limited adverse cytokine release in patients due to IL-15 sequestering within the overall TriKE protein construct. Such sequestering selectively delivers IL-15 directly to the immune synapse at the site of the cancer instead of being delivered throughout the entire body via intravenous systemic delivery – the typical delivery method for cytokine therapies. Such non-specific intravenous systemic delivery of cytokines can result in hyperactive T-cell responses leading to adverse cytokine storm release syndrome.

TriKE® addresses the most important aspects of the humoral (antibody) response against cancer, namely: (1) the ability of antibody to mediate antibody dependent cellular cytotoxicity (ADCC) through CD16, (2) the ability via IL-15 to mediate in vivo expansion of the immune population to recruit more NK cells and generate an anti-cancer response, and (3) recognition of a cancer cell’s target tumor antigen. With a scalable platform that offers the ability to target a variety of tumor cell markers, TriKE molecules can be used to treat both solid tumors and hematological cancers.

TriKE^® Clinical Pipeline

We have a diversified TriKE® therapeutic pipeline targeting several oncology indications and HIV.

Pipeline

GTB-3550 TriKE^®

GTB-3550 is the Company's first-generation TriKE product candidate that was initially evaluated in a first-in-human Phase 1 clinical trial for the treatment of relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and human IL-15. In the completed Phase 1 clinical study, GTB-3550 was shown to be safe and well-tolerated at the dose levels evaluated. The study of GTB-3550 demonstrates clinical proof of concept and provides a framework for the design of future clinical trials of TriKE product candidates.

GTB-3650 TriKE^®

GTB-3650 is being developed for the treatment of CD33 positive leukemias, including AML and MDS. GTB-3650 TriKE is the first TriKE product candidate under development that utilizes camelid nanobody technology. GTB-3650 TriKE is a tri-specific molecule composed of a camelid nanobody that binds the CD16 receptor on NK cells, a single chain variable fragment (scFv) that recognizes CD33 on tumor cells, and human IL-15. The IND application for GTB-3650 was cleared by the FDA in late June 2024.

GTB-5550 TriKE^®

The GTB-5550 TriKE product candidate is in development for the treatment of B7H3 positive solid tumor cancers. GTB-5550 TriKE is a tri-specific molecule composed of a camelid nanobody that binds the CD16 receptor on NK cells, the single chain variable fragment (scFv) of an anti-B7H3 antibody, and human IL-15.

GTB-4550 TriKE^®

The GTB-4550 TriKE product candidate is in development for the treatment of PD-L1 positive solid tumor cancers. GTB-4550 TriKE is a tri-specific molecule composed of a camelid nanobody that binds the CD16 receptor on NK cells, the single chain variable fragment (scFv) of an anti-PD-L1 antibody, and human IL-15.

GTB-6550 TriKE^®

The GTB-6550 TriKE product candidate is in development for the treatment of HER2 positive solid tumor cancers. GTB-6550 TriKE is a tri-specific molecule composed of a camelid nanobody that binds the CD16 receptor on NK cells, the single chain variable fragment (scFv) of an anti-HER2 antibody, and human IL-15.