Cullinan Oncology announces strategic expansion into autoimmune diseases

Cullinan Therapeutics 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 study. In a separate announcement, the company also announced a $280 million private placement. The proceeds from the private placement, combined with current cash, cash equivalents, short term investments and interest receivable, are expected to fund Cullinan’s current operating plan into 2028. Cullinan Therapeutics intends to pursue development of CLN-978 in autoimmune diseases, with systemic lupus erythematosus 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. 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. On April 8, 2024, the Journal of Experimental Medicine published a Found in Translation article highlighting the potential advantages of CD19-directed T cell engagers to be superior to CD19 CAR-T cell engaging antibodies relative to CD19 CAR-T cells for the treatment of autoimmune diseases. 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 undefined 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. 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.