Synthekine Presents New Phase 1a/1b IL-2 Data at SITC 39th Annual Meeting

Synthekine Inc., a company focused on engineered cytokine therapeutics, has shared promising translational results from the Phase 1a dose escalation segment of a Phase 1a/1b clinical trial for its innovative α/β-IL-2R biased partial agonist, STK-012. This announcement was made during the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in Houston. STK-012 is specially designed to selectively activate CD25+ antigen-activated T cells, which are known for their strong anti-tumor effects, while avoiding the broad stimulation of other lymphocytes such as natural killer (NK) cells, which can lead to IL-2-related toxicity. The ongoing Phase 1b dose expansion part of the study is currently treating adults with advanced solid tumors and includes the use of STK-012 in conjunction with standard care therapy for patients with PD-L1 negative non-small cell lung cancer (NSCLC).

Earlier this year, initial clinical results from the Phase 1a dose escalation section were presented at the American Association for Cancer Research (AACR), showing STK-012 to have a favorable safety profile, the absence of Capillary Leak Syndrome (CLS), and efficacy as a single agent in treating immuno-oncology (IO) refractory solid tumors. The latest findings presented at SITC build upon these initial results, further demonstrating STK-012's mechanism of action and its ability to selectively induce T cell activation and expansion.

The data presented at SITC included an analysis of key biomarkers, such as cytokine induction and the activation and expansion of memory CD8 T cells. These biomarkers were found to correlate with the best overall response (BOR). Additionally, the study highlighted the TCR clonal expansion observed with STK-012 monotherapy treatment, which led to an 80-fold median increase in expanding TCR clones. This TCR clonal expansion was also found to correlate with both progression-free survival (PFS) and BOR in the study participants.

Dr. Martin Oft, Chief Scientific Officer of Synthekine, expressed enthusiasm over the translational data for STK-012 monotherapy, noting that it signifies a significant advancement in cancer therapy. He highlighted that STK-012 is designed to harness the full potential of IL-2's efficacy while mitigating the severe toxicities typically associated with IL-2 treatments. Dr. Oft emphasized the reinforcement of STK-012’s unique mechanism, as evidenced by the selective expansion of antigen-activated T cells without broad expansion of other lymphocytes, including NK cells. Furthermore, he pointed out the strong and sustained induction of interferon gamma (IFNγ) with minimal increase in interleukin-6 (IL-6), supporting the efficacy and tolerability of STK-012. Synthekine is eager to advance this promising candidate to the next phase of clinical development.

Additionally, Synthekine presented two posters for STK-026, a biased IL-12 cytokine partial agonist. The preclinical data indicated that STK-026 is engineered to retain the potent antitumor activity of IL-12 while avoiding its systemic toxicities. A GLP toxicology study in cynomolgus monkeys showed that STK-026 has excellent tolerability and preferential activity toward CD8 T cells. Unlike unmodified IL-12 therapies, STK-026 is designed to bias immune activation toward the adaptive immune system and away from the innate immune system, thereby avoiding NK cell-mediated dose-limiting toxicities like cytokine release syndrome (CRS), hepatotoxicity, and lymphopenia.

Synthekine continues to focus on developing selective immunotherapies that improve the treatment paradigm for cancer and inflammatory diseases by leveraging insights into cytokine structure and function. Their goal is to unlock the full efficacy potential of cytokines while avoiding toxicities, using principles of cytokine partial agonism and immunological specificity across various protein engineering platforms to create a robust pipeline of product candidates. These novel immunotherapies include modified cytokines, cytokine-enhanced cell therapies, and surrogate cytokine agonists.