Nkarta (NKTX) H.C. Wainwright 4th Annual Cell Therapy Virtual Conference summary

Platform and program overview

• Developing a CD19-directed CAR-NK cell therapy with membrane-bound IL-15 for B-cell-mediated autoimmune diseases.

• Lead programs include Ntrust-1 for nephrology (lupus nephritis, primary membranous nephropathy) and Ntrust-2, a basket trial for systemic sclerosis, myositis, ANCA-associated vasculitis, and rheumatoid arthritis.

• Investigator-sponsored trials are ongoing in systemic lupus and myasthenia gravis.

• NK cell therapy aims to provide immune reset and long-term remission with a favorable safety profile, avoiding cytokine release syndrome and neurotoxicity.

• Therapy can be redosed safely, offering flexibility for relapsed or flaring patients.

Scientific rationale and translational work

• NK cells provide rapid, transient B-cell depletion, aligning with the need for early immune reset in autoimmune diseases.

• Translational studies monitor peripheral B-cell kinetics, BAFF elevation, and tissue/lymph node depletion to confirm mechanistic effects.

• Conditioning regimen evolved from cyclophosphamide alone to fludarabine plus cyclophosphamide for deeper B-cell depletion.

• Approach mirrors successful strategies in autologous CAR T trials.

Clinical trial design and endpoints

• Ntrust-1 (lupus nephritis) measures complete/partial renal response, proteinuria, complement, and anti-dsDNA as efficacy endpoints.

• Outpatient dosing allows broader patient access, with three doses of four billion cells each.

• Durability of remission and ability to re-treat are key goals; meaningful, durable complete renal responses are sought.

• Redosing is seen as a flexible option, not a chronic treatment.