Product Pipeline
We have a diversified TriKE™ therapeutic pipeline targeting several oncology indications.
Overview
GT Biopharma has developed a platform technology that engages the CD16 Fc receptor on NK cells, mediating tumor specific antigen targeting and an IL-15 moiety between them to induce NK cell proliferation and activation. Lead clinical programs are highlighted below. This platform technology can be applied to any known or proprietary tumor (or other target [e.g. HIV reservoirs]). Several are in research development or planned. The platform is based on the finding that the 2nd generation TriKE® are 10-40 times more potent than 1st generation TriKE and all TriKE development is now focused on this platform.
TriKE® Clinical Pipeline
GTB-3650 TriKE®
GTB-3650 is the company's first 2nd generation camelid nanobody TriKE® being tested clinically for the treatment of CD33 positive leukemias, including AML and MDS. GTB-3650 TriKE is the first TriKE clinical product that utilizes camelid nanobody technology. GTB-3650 TriKE is a Tri-specific Killer Engager 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 wild type IL-15. The IND application was cleared and enrollment started January 21, 2025. The ongoing Phase 1 dose escalation study is evaluating GTB-3650 for relapsed or refractory (r/r) CD33 expressing hematologic malignancies, including refractory acute myeloid leukemia and high-risk myelodysplastic syndrome. Enrollment in Cohort 4 (10 µg/kg/day) is ongoing, and the Company expects to initiate dosing in Cohort 5 (25 µg/kg/day) in Q2 2026. The Company anticipates providing the next update in the third quarter of 2026, which would include longer term follow-up on the six patients in Cohort 1 through 3 as well as initial observations from patients in Cohort 4 and Cohort 5. Dose escalation may continue up to Cohort 7 as necessary with the potential to evaluate GTB-3650 in a total of 14 patients (two patients per cohort). GTB-3650 is dosed in two-week blocks, two weeks on and two weeks off, for up to four months based on clinical benefit. The trial aims to assess the safety, pharmacokinetics, pharmacodynamics, in vivo expansion of endogenous patient NK cells and clinical activity. More details can be found on clinicaltrials.gov with the identifier: NCT06594445.
GTB-5550 TriKE®
GTB-5550 is a camelid (cam) anti-CD16/WT IL-15/cam anti-B7-H3 tri-specific natural killer (TriKE) cell engager, with a single chain recombinant TriKE® comprised of three components joined by flexible linkers: 1) a nanobody arm that engages the CD16 activating receptor (camelid anti-CD16) on natural killer (NK) cells; 2) a wildtype IL-15 (WT IL-15) linker arm to drive NK cell proliferation, priming, and survival; and 3) a nanobody arm that specifically engages B7-H3 (camelid anti-B7-H3) to target the antigen expressed on tumor cells.
The Phase 1 basket trial with GTB-5550 will be the first dual nanobody TriKE® tested with more patient-friendly subcutaneous dosing. The Phase 1a dose escalation portion of the trial will test up to 6 dose levels to identify the maximum tolerated dose (MTD). After the dose escalation phase, the Phase 2 expansion component of the trial will then confirm the MTD identified in the Phase 1a trial in up to seven different possible metastatic disease cohorts (castration-resistant prostate cancer, ovarian cancer, breast cancer, head and neck cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer) and further evaluate its safety, tolerability and preliminary anti-tumor activity. The Company remains well on track to initiate the trial in mid-2026.
GTB-5550 will be administered by subcutaneous (SQ) injection in the abdominal area for 5 consecutive days during Week 1 and Week 2 followed by 2 weeks of no treatment. One treatment cycle is 4 weeks in duration. A minimum of 2 cycles is planned, and patient-appropriate disease reassessment is performed after 2 cycles and every 8-12 weeks thereafter. Treatment may continue until disease progression, unacceptable toxicity, patient refusal, or treatment is no longer in the best interest of the patient. Patients are followed for 12 months to determine progression free survival (PFS) and overall survival (OS).
GTB-7550 TriKE®
The GTB-7550 TriKE product candidate is in development for the treatment of CD19 positive lymphoid malignancies and autoimmune disease. GTB-7550 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-CD19 antibody, and human wild type IL-15. GTB-7550 TriKE has been tested and published pre-clinically using models of lymphoma and chronic lymphocytic leukemia. Based on its early preclinical activity targeting normal B-cells, studies are ongoing to develop GTB-7550 in autoimmune disease.
GTB-3550 TriKE® (Supplanted by Second Generation GTB-3650)
GTB-3550 was the company's 1st clinical trial using a 1st generation TriKE product candidate that was initially evaluated in a 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 mutant IL-15. In the completed Phase 1 clinical study, GTB-3550 was shown to be safe and well-tolerated. The study of GTB-3550 demonstrated clinical proof of concept of in vivo activity. GTB-3550 and the 1st generation platform was discontinued after strong data suggested that the 2nd generation TriKE was more potent and exhibited better preclinical anti-tumor activity with camelid nanobody technology and wild type IL-15.