On October 28, 2021 Synthekine Inc., an engineered cytokine therapeutics company, reported it is advancing its IL-2 partial agonist, STK-012, into clinical investigation following clearance of its investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA) (Press release, Synthekine, OCT 28, 2021, View Source [SID1234592138]).

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Synthekine will evaluate STK-012 in a Phase 1a/1b, open-label, multi-center, dose escalation study. The study will investigate STK-012 both as a monotherapy and in combination with an immune checkpoint inhibitor in individuals with advanced solid tumors.

"IL-2 is a cytokine with proven benefit as an anti-cancer therapy. However, the indiscriminate activity of IL-2 can cause severe toxicities, limiting its clinical application," said Naiyer Rizvi, M.D., chief medical officer of Synthekine. "We have designed STK-012 to uncouple the efficacy and toxicity of IL-2, and we look forward to now investigating its potential in our first clinical development program."

STK-012 is designed as an alpha/beta-biased IL-2 partial agonist to selectively stimulate antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid stimulation of toxicity causing immune cells, such as natural killer cells. Synthekine has presented data at AACR (Free AACR Whitepaper) 2021 from preclinical studies demonstrating a mouse surrogate of STK-012 achieved superior tumor regression compared to both wild-type mouse IL-2 and a non-alpha-IL-2 agent, representing a different approach to biasing IL-2. In toxicity models, the mouse surrogate of STK-012, unlike these same comparators, was well tolerated and did not induce capillary leak syndrome (CLS), a dose-limiting IL-2-related toxicity which can result in death. In non-human primate models, STK-012 demonstrated a significantly improved pharmacokinetic and toxicity profile versus both aldesleukin (a recombinant IL-2 therapy) and a non-alpha-IL-2 agent.