MENLO PARK, Calif.--(BUSINESS WIRE)--Synthekine Inc., an engineered cytokine therapeutics company, today announced positive initial results from a first-in-human Phase 1 study (NCT05665062) of SYNCAR-001 + STK-009 for the treatment of relapsed or refractory CD19+ hematologic malignancies. In the results presented from 8 patients treated in the dose escalation portion of the study with a fixed SYNCAR-001 infusion of 30M cells and STK-009 doses ranging from 1.5 to 6 mg, this combination therapy was well tolerated with no dose-limiting toxicities (DLTs) or IL-2-related toxicities observed. This regimen also demonstrated durable responses, including complete responses in all 4 patients with non-Hodgkin lymphoma (NHL).
The data were presented by Lia Palomba, M.D., Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego. The poster will also be part of the ASH Poster Walk on Blood Immunology & Cellular Therapy: Advancing Innovations and Translational Insights hosted by Blood Immunology & Cellular Therapy today from 7:30 a.m. to 8:30 a.m. PT.
“Enhancing CAR-T cells with consistent cytokine support, particularly IL-2, has the potential to significantly improve their therapeutic effect. However, prolonged wild-type IL-2 administration is currently not feasible due to severe toxicities like capillary leak syndrome (CLS),” said Dr. Palomba. “SYNCAR-001 + STK-009 represents an innovative solution, enabling the targeted delivery of a potent and durable IL-2 signal specifically to CAR-T cells in vivo and avoiding activation and proliferation of native lymphocytes that can cause CLS. Based on the data presented at ASH, we are encouraged by SYNCAR-001 + STK-009’s favorable safety and efficacy profile and its potential to treat patients with relapsed or refractory B cell malignancies.”
SYNCAR-001 + STK-009 is a cytokine-enabled 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 (CAR-T) cell 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 data presented at ASH is important validation of our orthogonal IL-2 technology. Consistent with our preclinical observations, the combination of STK-009 and a low dose of SYNCAR-001 cells demonstrates robust cell expansion and persistence, potent cytotoxic activity, and durable cell fitness,” said Debanjan Ray, chief executive officer of Synthekine. “We are excited to report that STK-009 selectively delivered IL-2’s proliferation and activation signal to SYNCAR-001 cells without the toxicities, including CLS, that are typically associated with wild-type IL-2 treatment. Furthermore, the ability of STK-009 to provide an IL-2 signal exclusively to SYNCAR-001 cells may allow us to bypass the need for potentially toxic lymphodepleting chemotherapy (LDC). We are now enrolling patients to this trial without LDC and have recently opened a trial in autoimmune diseases also without LDC.”
SYNCAR-001 + STK-009 INITIAL PHASE 1 DOSE ESCALATION DATA IN CD19+ HEMATOLOGIC MALIGNANCIES
- As of the October 8, 2024, data cutoff, 8 patients have been treated in the dose escalation portion of the study. Following a standard regimen of cyclophosphamide/fludarabine (cy/flu), patients received a fixed dose of 30 million SYNCAR-001 cells and doses of STK-009 at 1.5 mg (n=3), 3 mg (n=3) and 6 mg (n=2)
- All patients were CAR-T naïve. Four patients had non-Hodgkin lymphoma (NHL) and four patients had chronic lymphocytic leukemia (CLL)
- Complete response (CR) was observed in all 4 patients with NHL, and 1 patient with CLL had stable disease (SD) as best overall response
- Responses were durable and ongoing in all 4 patients with NHL who exhibited CRs, with the longest duration of CR extending beyond 480 days
- Majority of adverse events (AEs) were Grade 1 or 2; the most common AEs were cytopenias expected to occur with cy/flu treatment
- Limited, mild-moderate cytokine release syndrome (CRS) was observed in 4 patients (maximum Grade 2); Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 1 patient
- A high proportion of SYNCAR-001 cells sustain a long-lasting central memory phenotype on STK-009 treatment
- Only minimal exhaustion and senescence of SYNCAR-001 cells was observed throughout the course of STK-009 treatment
In addition to this trial, a Phase 1 study (NCT06544330) of SYNCAR-001 + STK-009 in non-renal systemic lupus erythematosus and lupus nephritis is enrolling subjects, and received Fast Track designation from the U.S. Food and Drug Administration (FDA) in September 2024.
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.synthekine.com, and follow us on X @synthekine and LinkedIn.
