STK-009/SYNCAR-001 / Synthekine - LARVOL DELTA

A Phase 1 Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001) and Orthogonal IL-2 (STK-009) in Subjects with Relapsed or Refractory CD19 Expressing Hematologic Malignancies (NCT05665062) (ASH 2024) - P1 | "The objectives of the study are to evaluate the safety, efficacy, immunogenicity, and PK/PD of SYNCAR-001 + STK-009 with or without lymphodepleting chemotherapy (LDC; cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day on Day -5 to Day -3). Conclusions : This is the first reported clinical and translational data of an orthogonal cytokine system that provides a selective IL-2 signal to CAR T cells. Early results show that STK-009 administered with only 30×106 SYNCAR-001 CAR T cells has a favorable safety profile, durable efficacy, and meaningful SYNCAR-001 fitness, expansion and persistence."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • Richter's Syndrome • BCL2 • BCL6 • CD19 • CD27 • HAVCR2 • IFNG • IL15 • IL2 • IL6 • MYC

A Phase 1 Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001) and Orthogonal IL-2 (STK-009) in Subjects with Relapsed or Refractory CD19 Expressing Hematologic Malignancies (NCT05665062) (ASH 2024) - P1 | "The objectives of the study are to evaluate the safety, efficacy, immunogenicity, and PK/PD of SYNCAR-001 + STK-009 with or without lymphodepleting chemotherapy (LDC; cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day on Day -5 to Day -3). Conclusions : This is the first reported clinical and translational data of an orthogonal cytokine system that provides a selective IL-2 signal to CAR T cells. Early results show that STK-009 administered with only 30×106 SYNCAR-001 CAR T cells has a favorable safety profile, durable efficacy, and meaningful SYNCAR-001 fitness, expansion and persistence."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • Richter's Syndrome • BCL2 • BCL6 • CD19 • CD27 • HAVCR2 • IFNG • IL15 • IL2 • IL6 • MYC

A Phase 1 Study of SYNCAR-001 + STK-009 Without Conditioning Chemotherapy (Lymphodepletion) in Subjects With Severe, Refractory Systemic Autoimmune Rheumatic Disease (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Synthekine | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Orthogonal IL-2/IL-2R β Armoring is Superior to TGF-β Receptor Blockade in Overcoming TGF-β-Driven Inhibition of GPC3 CAR T Cells in Hepatocellular Carcinoma (ASGCT 2025) - P1 | "STK-009/SYNCAR-002 treatment demonstrated superior tumor control, cell proliferation, and better cell fitness compared to the DNTGFBRII armored CAR T cells. These findings support the advantage of an orthogonal IL-2/IL-2R system that selectively drives and sustains potent T cell effector function even in an adverse tumor microenvironment saturated with TGF-β. Disease Focus of Abstract:Cancer Solid Tumors"

CAR T-Cell Therapy • Hematological Malignancies • Hepatocellular Cancer • Lymphoma • Oncology • Solid Tumor • IFNG • IL2RA • TGFB1

STK-009-101: Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Synthekine | Recruiting ➔ Active, not recruiting

Enrollment closed • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With Severe, Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Synthekine | Initiation date: Dec 2024 ➔ Mar 2025

Trial initiation date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Synthekine Presents Positive Initial Results from Phase 1 Clinical Trial of CD19 CAR-T (SYNCAR-001) and Orthogonal IL-2 (STK-009) Combination Therapy for Treatment of Hematologic Malignancies at ASH 2024 Annual Meeting (Businesswire) - P1 | N=36 | NCT05665062 | Sponsor: Synthekine | "Synthekine...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.....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....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."

P1 data • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

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 (ACR Convergence 2024) - P1 | "These findings support clinical exploration of SYNCAR-001 + STK-009 in AI diseases like SLE and RA to achieve CD19 CAR T expansion and significant B cell aplasia without genotoxic, lymphodepleting agents. SYNCAR-001 + STK-009 is in Phase I trials for heme malignancies (NCT05665062), with LN and SLE patient enrollment expected later this year."

CAR T-Cell Therapy • IO biomarker • Preclinical • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Lymphoma • Nephrology • Oncology • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus • CD19 • IL2RA

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects with Severe, Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Synthekine | Initiation date: Sep 2024 ➔ Dec 2024

CAR T-Cell Therapy • Trial initiation date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

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 (Businesswire) - "Synthekine....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. 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."

Preclinical • Immunology • Rheumatoid Arthritis • Systemic Lupus Erythematosus

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With Severe, Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Synthekine | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Synthekine Granted U.S. FDA Fast Track Designation for CD19 CAR-T and Orthogonal IL-2 Investigational Therapy, SYNCAR-001 + STK-009, for the Treatment of Lupus Without Lymphodepletion (Businesswire) - "Synthekine...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to SYNCAR-001 + STK-009, its CD19 CAR-T and orthogonal IL-2 investigational therapy, for the treatment of patients with severe, refractory systemic lupus erythematosus (SLE), without the use of lymphodepletion....The FDA recently cleared an IND application for a Phase 1 study (NCT06544330) of SYNCAR-001 + STK-009 in non-renal SLE and lupus nephritis (LN)....The multi-center, dose escalation clinical trial will assess the safety and clinical activity of SYNCAR-001 + STK-009 in patients with non-renal SLE and LN."

Fast track • Trial status • Lupus Nephritis • Systemic Lupus Erythematosus

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With Severe, Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Synthekine

CAR T-Cell Therapy • New P1 trial • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Orthogonal IL-2/IL-2Rβ signaling selectively enhances and sustains a synthetic effector state via a novel mechanism and outperforms constitutive armoring approaches (AACR 2024) - P1 | "In a HCC tumor model, treatment with STK-009/SYNCAR-002 demonstrated superior tumor control with minimal toxicities. Interestingly, IL-18 overexpression also controlled tumors, but was accompanied by uncontrolled CAR T cell expansion and toxicity resembling severe GVHD.scRNAseq analyses revealed STK-009-treated SYNCAR-002 T cells simultaneously activated effector genes and repressed an exhaustion gene signature. This analysis also identified a novel mechanism by which STK-009/oRβ signaling induces a superior synthetic effector state via transcriptional repression of the stress response/proteosome.These findings support the advantages of an orthogonal platform that selectively drives and sustains potent T cell effector function without safety concerns associated with constitutively expressed armored approaches."

Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Lymphoma • Oncology • Solid Tumor • GPC3 • IL15 • IL18 • IL2 • IL2RA • JUN

Synthekine Cleared to Tackle Lupus With CAR-T and IL-2 Combination Therapy in US Clinical Trial (CGTLive) - "'Recent studies have shown that CD19-targeted cell therapies can make a meaningful impact on nonrenal SLE, LN, and other autoimmune conditions,' Naiyer Rizvi, MD...said in a statement. 'However, successful treatment with CD19 CAR-Ts requires patients to be lymphodepleted, a significant burden on the patient, physician, and healthcare system. By leveraging Synthekine's orthoIL-2 technology, STK-009 has the potential to drive SYNCAR-001 cell engraftment and controlled cell expansion without lymphodepletion. We look forward to bringing our highly differentiated treatment option to patients.'"

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Synthekine Announces U.S. FDA Clearance of IND Application for CD19 CAR-T and Orthogonal IL-2 Combination Therapy, SYNCAR-001 + STK-009, for Treatment of Lupus Without Lymphodepletion (Businesswire) - "Synthekine...today announced that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application to evaluate SYNCAR-001 + STK-009, its orthogonal IL-2 and CD19 CAR-T combination therapy, in patients with non-renal systemic lupus erythematosus (SLE) and lupus nephritis (LN), without the use of any lymphodepletion....The multi-center, dose escalation clinical trial will assess the safety and clinical activity of SYNCAR-001 + STK-009 in patients with non-renal SLE and LN....The first patient is expected to be enrolled in the second half of 2024."

IND • New trial • Lupus Nephritis • Systemic Lupus Erythematosus

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Synthekine | Trial primary completion date: Jun 2024 ➔ Jun 2026

CAR T-Cell Therapy • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Synthekine

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Synthekine | Initiation date: Feb 2023 ➔ Jun 2022

Trial initiation date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Engineered human IL-2/IL-2Rß orthogonal pairs selectively enhance anti-GPC3 CAR T cells in vivo to drive complete responses in solid epithelial tumor models (SITC 2023) - P1 | "Importantly, STK-009 induced the expression of cytotoxic machinery, pro-survival, and proliferative genes in tumor-infiltrating SYNCAR-002 (figure 3). Conclusions These findings validate that the orthogonal IL-2 platform has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo and activating CAR-T cells in a hostile tumor microenvironment."

CAR T-Cell Therapy • IO biomarker • Preclinical • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Lymphoma • Oncology • Solid Tumor • CD19 • GPC3 • IL2

Study of SYNCAR-001 and STK-009 Begins in CD19+ Hematologic Malignancies (Targeted Oncology) - "'While CAR T-cell therapies have had a major impact for patients with CD19+ hematologic malignancies, only a subset of these patients have durable benefit,' said Naiyer Rizvi, MD...'We believe that controllable, selective and sustained cytokine support is central to the advancement of this class of treatment, and STK-009 plus SYNCAR-001 has the potential to drive deeper and more durable responses while avoiding serious toxicities related to uncontrolled CAR T-cell expansion for patients in need of better treatment options.'"

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Synthekine Doses First Patient in Phase 1 Clinical Trial of Orthogonal IL-2 and CD19 CAR-T Combination Therapy, STK-009 + SYNCAR-001, for Treatment of CD19+ Hematologic Malignancies (Businesswire) - "'While CAR-T cell therapies have had a major impact for patients with CD19+ hematologic malignancies, only a subset of these patients have durable benefit,' said Naiyer Rizvi...'We believe that controllable, selective and sustained cytokine support is central to the advancement of this class of treatment, and STK-009 + SYNCAR-001 has the potential to drive deeper and more durable responses while avoiding serious toxicities related to uncontrolled CAR-T cell expansion for patients in need of better treatment options.'"

Media quote

Synthekine Doses First Patient in Phase 1 Clinical Trial of Orthogonal IL-2 and CD19 CAR-T Combination Therapy, STK-009 + SYNCAR-001, for Treatment of CD19+ Hematologic Malignancies (Businesswire) - "Synthekine Inc...announced that the first patient has been dosed in a Phase 1 clinical trial of its orthogonal IL-2 and CD19 CAR-T combination therapy, STK-009 + SYNCAR-001, in adults with relapsed or refractory CD19+ hematologic malignancies....The first-in-human Phase 1 clinical trial of SYNCAR-001 + STK-009 is an open-label, multi-center study enrolling patients with CD19+ hematologic malignancies."

Trial status • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase 1 study to evaluate the safety and tolerability of a combination autologous CD19 CAR T cell therapy (SYNCAR-001) and orthogonal IL-2 (STK-009) in subjects with relapsed or refractory CD19 expressing hematologic malignancies (NCT05665062) (AACR 2023) - P1 | "Secondary endpoints include assessments of response, pharmacokinetics, and immunogenicity. Exploratory endpoints include assessment of immune cell populations, and relevant gene/protein expression, as well as persistence, phenotype, and functionality of SYNCAR-001 in the peripheral blood and/or bone marrow in response to STK-009."

CAR T-Cell Therapy • Clinical • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • CD19 • IL2

Synthekine Announces Presentations at AACR 2023 Annual Meeting Showcasing Next Series of Oncology Programs (Businesswire) - "Synthekine...announced that two poster presentations showcasing its next series of oncology programs will be delivered at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023....'We are introducing the clinical trial design for our orthogonal IL-2 and CD19 CAR-T combination therapy, STK-009 + SYNCAR-001'....The objectives of this study are to evaluate the safety, preliminary efficacy, pharmacokinetics, immunogenicity, and pharmacodynamics of SYNCAR-001 + STK-009. Recruitment in the Phase 1 study is underway."

Trial status • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology