GTB-3550 TRIKE

As proof of concept, a clinical trial of GTB-3550 (a CD33-targeted Tri-specific Killer Engager [TriKE] in AML) induced endogenous NK cell expansion and activation in refractory AML patients. Here we developed GTB-5550 (a B7H3 TriKE) as a novel dual camelid (cam) TriKE containing WT IL-15 and comprised of two cam engagers: targeting CD16 on NK cells and B7H3 on multiple solid tumors...Conclusions B7H3 TriKE delivers an NK cell specific IL-15 signal to expand NK cells and is highly specific against a broad array of cancers. Clinical manufacturing is underway with an IND planned to open clinical trials in 2023 in a number of solid tumors and multiple myeloma.

P1/2, N=12, Terminated, GT Biopharma, Inc. | N=60 --> 12 | Trial completion date: Aug 2025 --> Sep 2021 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2024 --> Aug 2021; Development of GTB-3550 halted due to development of the second generation camelid nanobody TriKE drug product, GTB-3650.

NK cell degranulation and IFN-gamma production of GTB-3550-treated samples were higher compared to that of control samples treated with B7H3 single domain or IL-15 alone. Ongoing experiments will evaluate functionality of GTB-5550 on FA patient samples as well as in spheroid assays. Taken together, this data shows that a GTB-5550 is able to drive NK cell activity against B7H3-expressing HNSCC cells, which presents potential for a B7H3-targeted TriKE to be used to be implemented clinically to treat HNSCC or FA-HNSCC patients.

P1/2, N=60, Active, not recruiting, GT Biopharma, Inc. | Recruiting --> Active, not recruiting

GTB-3550 TriKE given as a monotherapy safely induced a sustained functional expansion of endogenous NK cells with anti-tumor activity in advanced AML and MDS patients treated with at least 25 mcg/kg/day. Second generation solid tumor TriKE therapeutics against HER2 and B7H3 will be tested clinically next year.

Gemtuzumab ozogamicin was the first and only CD33-directed antibody-drug conjugate to be US Food and Drug Administration approved for AML...Promising new strategies include cellular therapy mechanisms and linker molecules. This is an exciting target that requires a considerable amount of precision to yield clinical benefit.