Cullinan Therapeutics, Inc. announced important updates about its plan to expand into autoimmune diseases, the scientific rationale for developing CLN-978 in autoimmune diseases, and initial clinical observations from its B cell non-Hodgkin lymphoma (B-NHL) study. Cullinan Therapeutics intends to pursue development of CLN-978 in autoimmune diseases, with systemic lupus erythematosus (SLE) as a first indication. The company believes that CLN-978 has the potential to be a first-in-class, off-the-shelf, disease-modifying treatment in autoimmune diseases with a differentiated safety profile?.

The company plans to submit an investigational new drug application to study CLN-978 in patients with SLE in the third quarter of 2024 and is also planning for future development in other autoimmune diseases. The company has discontinued enrollment in its B-NHL study to focus ongoing development on autoimmune indications. Recent data demonstrated the potential of CD19 directed CAR T therapies in the treatment of 15 patients with autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myositis, systemic sclerosis).1 While the efficacy was notable, challenges could limit broad uptake of CAR T therapy, such as the requirement for lymphodepleting chemotherapy, risk of secondary malignancies, complex manufacturing processes, and limited patient access.

CD19-directed therapies afford significant potential for the breadth of B cell depletion and the necessary immune reset, since CD19 expression occurs across all B lineage cells, including the short-lived plasma cells and plasmablasts that produce the pathogenic autoantibodies present in autoimmune conditions. The company believes that CLN-978 could offer a novel solution for patients and providers as a T cell engager designed to deliver potency with off-the-shelf convenience and subcutaneous dosing?. Clinical observations from three patients treated in a Phase 1 dose escalation trial of patients with B-NHL show that CLN-978 was clinically active at the initial starting dose of 30 µg administered subcutaneously once weekly.

Two of the three patients experienced objective clinical benefit including one patient who experienced a complete response. Grade 1 cytokine release syndrome occurred in two patients and no patients experienced immune effector cell-associated neurotoxicity syndrome. Other adverse events were low-grade, manageable, or mechanistically based (e.g. transient lymphopenia after the first dose only)?.

Of the two patients with detectable B cells at baseline, both patients experienced rapid, deep, and sustained B cell depletion after administration of CLN-978. These data show that CLN-978 can deplete peripheral B cells and demonstrate clinical activity in a tissue resident disease at a dose with a favorable safety profile.