Synthekine to Present Preclinical Data for CD19 CAR-T (SYNCAR-001) Empowered by Orthogonal IL-2 (STK-009) Without Lymphodepletion at American College of Rheumatology (ACR) Convergence 2024

Co-dosing of murine surrogates of STK-009 and SYNCAR-001 in a lymphoreplete mouse model of SLE demonstrated robust CAR-T cell expansion and elimination of severe proteinuria

Co-dosing of murine surrogates of STK-009 and SYNCAR-001 in a lymphoreplete mouse model of RA led to complete B cell depletion in the joints along with synovial restoration

MENLO PARK, Calif.--(BUSINESS WIRE)--Synthekine Inc., an engineered cytokine therapeutics company, today announced promising preclinical results with the murine version of its STK-009 + SYNCAR-001 program will be presented at the American College of Rheumatology (ACR) Convergence 2024 in Washington, D.C. This regimen demonstrated potential to treat autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), without requiring lymphodepletion.

Preclinical findings to be presented at ACR highlight that co-administration of murine (m) STK-009 and SYNCAR-001 effectively depleted CD19+ B cells and achieved curative efficacy in both SLE and RA mouse models without lymphodepletion. Across both models, mSTK-009 provided controllable, selective and sustained cytokine support to enable expansion and activation of mSYNCAR-001 cells.

• In the non-lymphodepleted SLE model, mSTK-009 + mSYNCAR-001 reduced autoantibody production and reversed severe proteinuria, indicating an improvement in kidney function.
• In the non-lymphodepleted RA model, mSTK-009 + mSYNCAR-001 depleted CD19+ B cells in affected joints, restored synovia, and reversed arthritis.

In the absence of mSTK-009 driven cytokine support, the efficacy of mSYNCAR-001 was significantly reduced in these lymphoreplete models.

“CD19 CAR-Ts have the potential to be transformative in autoimmune diseases such as SLE and RA,” said Debanjan Ray, chief executive officer of Synthekine. “However, traditional CD19 CAR-Ts require lymphodepleting chemotherapy, which carries significant toxicities for the patient. The data we are presenting at ACR demonstrate that STK-009 + SYNCAR-001 can deliver efficacy without lymphodepletion in SLE and RA mouse models, and we are excited to bring this highly differentiated treatment option to patients. The clinical study for STK-009 + SYNCAR-001 in non-renal SLE and lupus nephritis (LN) is currently enrolling subjects, and we are exploring expanding into other autoimmune indications as well.”

STK-009 + SYNCAR-001 is a cytokine-inducible cell therapy regimen based on Synthekine’s proprietary orthogonal IL-2 technology. It is a two-component therapy consisting of SYNCAR-001, an autologous CD19-targeting chimeric antigen receptor T cell (CAR-T) which expresses an engineered IL-2 receptor, and STK-009, an engineered pegylated IL-2 cytokine that selectively signals through the engineered IL-2 receptor. The STK-009 + SYNCAR-001 combination therapy is currently being evaluated in a Phase 1 study (NCT05665062) in CD19+ hematologic malignancies and a Phase 1 study (NCT06544330) in non-renal SLE and LN. STK-009 + SYNCAR-001 received Fast Track designation from the U.S. Food and Drug Administration (FDA) in September 2024 for the treatment of patients with severe, refractory SLE, without the use of lymphodepletion.

Details are as follows and available on the ACR website:

Title: SYNCAR: An Engineered IL-2/IL-2R-system That Selectively Enhances CD19 CAR T Cells to Deplete B Cells and Provide Therapeutic Benefit in SLE and RA Mouse Models Without Lymphodepletion
Session: SLE – Animal Models Poster
Session Date & Time: Saturday, November 16, 2024, 10:30 AM – 12:30 PM ET
Session Type: Poster Session A
Abstract Number: 0087

A copy of the poster will be available on Synthekine’s website following presentation at the meeting.

About Synthekine

Synthekine is harnessing the potential of cytokine therapeutics to develop selective immunotherapies designed to improve the treatment paradigm of cancer and inflammatory disease. Using insights on cytokine structure and function, the company engineers therapeutics designed to unlock the full efficacy potential of cytokines while avoiding their associated toxicities. Synthekine is applying principles of cytokine partial agonism and immunological specificity across multiple protein engineering platforms to create a broad and deep pipeline of product candidates. These novel immunotherapies include modified cytokines, cytokine-enhanced cell therapies and surrogate cytokine agonists. For more information, visit www.www.synthekine.com, and follow us on X @synthekine and LinkedIn.