Autoimmunity

AlloNK® + Rituximab in Lupus Nephritis

Systemic lupus erythematosus (SLE) is a chronic, potentially severe, autoimmune disease characterized by abnormal B-cell function and autoantibody production resulting in a range of clinical manifestations including end organ damage and an increased risk of death. SLE affects an estimated 200,000 patients in the U.S [1]. Lupus nephritis (LN) is the most common end-organ manifestation of SLE, affecting approximately 40% of SLE patients, and more than 40% of patients with the most severe LN will develop end-stage renal disease requiring dialysis and transplant within 15 years [2].

Seminal clinical data has been generated using autologous CAR-T cells suggesting that a deep B-cell depletion can induce complete and long-lasting responses in patients with LN. However, the use of autologous CAR-T cells requires apheresis, likely hospitalization, and the potential for serious side effects. Rituximab alone has been shown to produce incomplete B-cell depletion, whereas addition of AlloNK as an ADCC-enhancing therapy could significantly improve rituximab’s ability to drive deeper levels of B-cell depletion.

We are investigating the safety and clinical activity of AlloNK in combination with rituximab for treatment of SLE in patients with active LN. AlloNK is the first allogeneic, off-the-shelf NK or CAR-T cell therapy candidate to receive an IND clearance in autoimmune disease. With our modular approach, we are investigating AlloNK in preclinical models in combination with other monoclonal antibodies and in additional autoimmune indications.

[1] US CDC, National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)

[2] Tian et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. 2023 Mar;82(3):351-356. doi: 10.1136/ard-2022-223035.

Expanded Access Policy