Synthekine, Inc.

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 66 th 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 .

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 .

MENLO PARK, Calif.--( BUSINESS WIRE )-- Synthekine Inc ., an engineered cytokine therapeutics company, today presented positive translational results from the Phase 1a dose escalation portion of a Phase 1a/1b clinical trial of its first-in-class α/β-IL-2R biased partial agonist, STK-012, at the Society for Immunotherapy of Cancer (SITC) 39 th Annual Meeting in Houston. STK-012 is engineered to selectively stimulate CD25+ antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid broad stimulation of other lymphocytes, such as natural killer (NK) cells, which are associated with IL-2 toxicity. The Phase 1b dose expansion portion of the study in adults with advanced solid tumors remains ongoing ( NCT05098132 ) and will include treating patients with STK-012 in combination with standard of care therapy in first line PD-L1 negative non-small cell lung cancer (NSCLC). Initial clinical findings for STK-012 monotherapy from the Phase 1a dose escalation portion of the study were presented at AACR earlier this year , showing a favorable safety profile without Capillary Leak Syndrome (CLS) and with single agent efficacy, including multiple objective responses, in IO-refractory solid tumors. The findings shared at SITC build on these monotherapy results from the same study population, further demonstrating the mechanism of action of STK-012 and its ability to selectively induce T cell activation and expansion. Results presented in the STK-012 poster at SITC include an analysis of key biomarkers, such as cytokine induction and memory CD8 T cell activation and expansion, both of which were found to correlate with best overall response (BOR). The poster also includes analysis of the TCR clonal expansion observed upon treatment with STK-012 monotherapy, which led to an 80-fold median increase in expanding TCR clones. TCR clonal expansion was found to correlate with both progression-free survival (PFS) and BOR in these patients. “ We are very encouraged by the translational data for STK-012 monotherapy as it represents a powerful advancement in cancer therapy, designed to realize the full efficacy potential of IL-2 while eliminating severe toxicities typically associated with IL-2 treatment,” said Martin Oft, M.D., chief scientific officer of Synthekine. “ Our data reinforces STK-012’s unique mechanism of action, as demonstrated by selective expansion of antigen activated T cells without broad expansion of other lymphocytes including NK cells. In addition, we see strong and sustained induction of interferon gamma (IFNγ) coupled with minimal increase of interleukin-6 (IL-6), supporting the efficacy and tolerability profile of STK-012. We look forward to advancing this promising candidate to the next stage of clinical development.” The company will also present two posters for STK-026, a biased IL-12 cytokine partial agonist. The preclinical data to be presented demonstrates STK-026 is engineered to retain the potent antitumor activity of IL-12 while avoiding its systemic toxicities. In addition, results of a GLP toxicology study in cynomolgus monkeys showed excellent tolerability of STK-026 and confirmed its preferential activity toward CD8 T cells. Relative to therapies based on unmodified IL-12, STK-026 is tuned to bias immune activation toward the adaptive and away from the innate immune systems, thus avoiding NK cell mediated dose-limiting toxicities that are the hallmark of IL-12 therapy, including cytokine release syndrome (CRS), hepatoxicity, and lymphopenia. Details are as follows and available on the SITC website : Title : T cell and Immune Activation from a Phase 1 Study of STK -012, a First-in-class IL-2R α/ß Selective Partial Agonist in Advanced Solid Tumors Session Name: Novel Single-Agent Immunotherapies Session Date & Time : Friday, November 8, 2024, 9:00 AM – 7:00 PM CT Format: Poster Presentation Abstract Number : 1325 Title : STK -026, a detoxified IL-12 partial agonist is well-tolerated and sustains CD8+ T cell activity with repeat doses in cynomolgus macaques Session Name: Immune-Stimulants and Immune Modulators Session Date & Time : Friday, November 8, 2024, 9:00 AM – 7:00 PM CT Format: Poster Presentation Abstract Number : 941 Title : Gradual lymphocyte activation with IL-12 partial agonist STK-026 maintains anti-tumor efficacy but escapes acute NK-mediated cytokine release and toxicities associated with WT IL-12 Session Name: Immune-Stimulants and Immune Modulators Session Date & Time : Saturday, November 9, 2024, 9:00 AM – 8:30 PM CT Format: Poster Presentation Abstract Number : 964 Copies of the posters 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.synthekine.com , and follow us on X @synthekine and LinkedIn .