CLN-049

P1, N=60, Recruiting, Cullinan Therapeutics Inc. | Trial completion date: Nov 2025 --> Jun 2027 | Trial primary completion date: Aug 2025 --> Jan 2027

First-generation multi-kinase inhibitors like midostaurin and second-generation agents such as gilteritinib and quizartinib have shown success. It discusses how these agents, including small-molecule like STI-8591, compounds 36 and 80 and novel therapeutic strategies such as CLN-049, and SENTI-202, are designed to combat resistance. The goal is to provide a medicinal chemistry perspective to provide insights for the design of novel small-molecule FLT3i.

Eligible pts include adults with AML R/R to standard induction chemotherapy or venetoclax-based regimens and MDS R/R to hypomethylating agents (HMA)-based treatment...The first pt (baseline 47% BM blasts and receiving hydroxyurea to control leukocytosis) experienced Grade 2 CRS 5.5 hours after infusion that resolved within 24 hours with supportive care... Safety and PK data from the SAD portion supported initiation of the MAD study. Measurable cytokine induction consistent with biological activity was observed at the initial IV dose level tested. Enrollment to the Part C SC dose escalation is ongoing, and updated data will be presented.

CLN-049 has a favorable efficacy and safety profile in preclinical models, warranting evaluation of its antileukemic activity in the clinic.

In summary, CLN-049 is a promising FLT3-targeted T cell engaging antibody construct expected to have robust anti-tumor activity in the clinic against AML. CLN-049 is currently in a phase 1 clinical trial for the treatment of patients with relapsed/refractory AML.

P1, N=9, Recruiting, Cullinan Oncology, LLC