Positive preclinical data for novel CD19xCD3 T cell engager CLN-978 have supported its potential as a new therapeutic option for autoimmune diseases.

Cullinan Therapeutics presented the preclinical results and a study schema for a planned Phase Ib study in patients with moderate to severe systemic lupus erythematosus (SLE) at the annual meeting of the American College of Rheumatology (ACR) Convergence 2024 in Washington, DC.

The new in vitro preclinical data show CLN-978 induced similar T cell activation, target B cell depletion, and cytokine production in human peripheral blood mononuclear cells (PBMC) derived from patients with SLE or rheumatoid arthritis (RA) as compared to healthy volunteers.

These studies collectively suggest that the previously observed cytokine window observed in B-NHL model systems, potentially resulting in a broad therapeutic index, is expected to be preserved in SLE and RA patients.

“These new preclinical data further demonstrate that CLN-978 is a highly potent T cell engager. With the ability to be subcutaneously delivered, CLN-978 offers off-the-shelf convenience while achieving significant B cell depletion, supporting its potential as a promising new therapeutic option for autoimmune diseases,” said Jeffrey Jones, Chief Medical Officer of Cullinan Therapeutics.

In October, Cullinan Therapeutics announced US Food and Drug Administration (FDA) clearance of an Investigational New Drug Application for its global Phase I clinical trial to evaluate CLN-978 for the treatment of patients with moderate to severe SLE. The company previously announced Human Research Ethics Committee approval to initiate the global clinical trial in Australia.

Small in molecular size (65 kDa), CLN-978 contains two single-chain variable fragments, one binding with very high affinity to the CD19 target and the other binding to CD3 on T cells, and a single-domain antibody binding to human serum albumin to extend serum half-life.

Diana Spencer, Senior Digital Content Editor, DDW