Treatment with STK-012 monotherapy demonstrates dose-dependent induction of pro-inflammatory cytokines and selective proliferation of antigen-activated T cells, along with significant expansion of TCR clonality

Company will also present new preclinical and GLP toxicology data on STK-026, its biased IL-12 partial agonist also designed for preferential activity on antigen-activated T cells

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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20241108163003/en/