Cambridge, Massachusetts-based CREATE Medicines, Inc. has received Human Research Ethics Committee (HREC) approval in Australia to begin a first-in-human Phase I/II study of CRT-402, an in vivo CD19-directed CAR-T therapy for systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myopathies. The approval clears the final regulatory hurdle before patient enrollment and marks CREATE's first clinical program outside oncology.
CRT-402 is delivered via CREATE's proprietary mRNA-lipid nanoparticle (mRNA-LNP) platform, which encodes a CD19-targeting CAR and programs the patient's circulating T cells directly within the body — bypassing the leukapheresis, viral vector engineering, and ex vivo expansion that conventional CAR-T manufacturing requires. The mRNA payload degrades naturally, producing transient CAR expression rather than persistent T cell engraftment, a property the company considers advantageous in autoimmune settings where a defined pulse of B cell depletion — followed by tolerogenic B cell reconstitution — is the therapeutic objective.
A 2024 New England Journal of Medicine case series reported that a single infusion of CD19-directed CAR-T cells produced clinical remission across all three disease categories in 15 patients who had failed standard therapies, with patients able to discontinue immunosuppression entirely.
Unlike CD20-targeting antibodies such as rituximab, CD19 CAR-T therapies also eliminate plasmablasts and some plasma cells that continue producing pathogenic autoantibodies, making them attractive candidates for immune reset in refractory autoimmune disease.
Several companies, including Bristol Myers Squibb, Kyverna, Cabaletta and Capstan Therapeutics, are developing CD19 CAR-T therapies for autoimmune disease. Unlike Bristol Myers Squibb, Kyverna and Cabaletta, which use conventional ex vivo manufacturing, CREATE and Capstan are pursuing in vivo delivery designed to eliminate cell manufacturing altogether.