MENLO PARK, Calif.--(BUSINESS WIRE)--Synthekine Inc., an engineered cytokine therapeutics company, today presented new data from preclinical studies of STK-026, its biased IL-12 partial agonist program, during the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting in San Diego. STK-026 is designed to retain the potent antitumor activity of IL-12 while avoiding its systemic toxicities and is currently in IND-enabling studies.
“In the quest for developing new and effective cancer treatments, the pro-inflammatory cytokine IL-12 has shown tremendous potential but clinical use of IL-12 is limited by systemic toxicities and a very narrow therapeutic window,” said Martin Oft, M.D., chief scientific officer of Synthekine. “Through our deep insights into the biology of IL-12 and our industry-leading cytokine engineering capabilities, we designed STK-026 to uncouple efficacy from the toxicities that are typically seen with wild-type IL-12. The data presented today adds to the growing body of evidence that STK-026’s novel approach, biasing IL-12’s activity toward activated T cells and avoiding hyperactivation of NK cells, has potential to harness anti-tumor efficacy without dose-limiting toxicity.”
Title: Preclinical Pharmacodynamic Characterization of STK-026: A Novel IL-12 Partial Agonist for Cancer with Maintained CD8 T cell activity, Reduced NK-mediated Toxicity and an Improved Therapeutic Window
Session Title: Immune-Stimulants and Immune Modulators
Session Date & Time: Friday, Nov. 3, 2023, 9 am – 7 pm PT
Poster Board Number: 1053
Summary & Key Findings:
- STK-026 is a biased IL-12 agonist engineered to exhibit preferential activity on antigen-activated T cells, which drive the efficacy of IL-12, while avoiding broad systemic activation of resting T cells and NK cells, which are linked to the toxicity of IL-12.
- In tumor bearing mouse models, a mouse surrogate of STK-026 was well-tolerated and showed meaningful anti-tumor efficacy as both a single agent and in combinations. Notably, compared to wild-type IL-12 treatment, STK-026 monotherapy demonstrated a substantial improvement in therapeutic window which was associated with reduced NK activation and systemic cytokine induction.
- In cynomolgus macaques, STK-026 was well-tolerated at very high doses (up to 5mg/kg) without signs of CRS. Further, compared to wild-type IL-12, STK-026 treatment resulted in reduced induction of liver enzymes, organ weight gains and lymphocyte activation in peripheral tissues, thus avoiding the detrimental toxicity associated with IL-12 therapy.
- Overall, assessments of STK-026 in mouse and cyno show that its properties successfully avoid spikes of early NK activation but still effectively activate T cells. Preclinical studies and pharmacology support the idea that this rebalancing of IL-12 driven innate and adaptive immune responses can achieve efficacy without dose-limiting toxicity.
The poster will be available on Synthekine’s website following presentation at the meeting.
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 Twitter @synthekine and LinkedIn.