Exicure is set to move toll-like receptor 9 (TLR9) agonist AST-008 into a phase 1b/2 trial after getting a look at data from healthy volunteers. The first-in-human clinical trial suggested that AST-008 is safe, tolerable and boosts cytokine levels.
AST-008, Exicure’s lead asset, is based on the same spherical nucleic acid (SNA) platform as the rest of the biotech’s pipeline. When applied to cancer, Exicure thinks the platform will lead to long, strong innate immune responses, making it a better bet in oncology than traditional immunostimulatory oligonucleotide-based approaches.
That idea remains unproven, but Exicure is starting to generate clinical data to test its hypothesis. The first AST-008 data drop comes from a single ascending dose trial of 16 healthy volunteers. None of the participants suffered serious adverse events or dose-limiting toxicities.
The safety and tolerability assessment was the core focus of the trial, but Exicure also looked for signs AST-008 is acting on TLR9. As the protein is involved in the production of cytokines, Exicure assessed how levels of these immune-cell secretions changed following administration of AST-008. Among the four people who took the highest dose, Exicure saw two to 57-fold increases in the levels of different cytokines.
While the implications of the findings for efficacy remain unclear, Exicure’s cytokine data compares favorably to results gathered in early-phase trials of Mologen’s lefitolimod and Pfizer’s PF-03512676. That has encouraged Exicure to advance AST-008.
“Phase 1 results for AST-008 demonstrated our desired highly potent immune system activation without serious adverse events or dose limiting toxicity. We believe this molecule could lead to better combination therapies for patients with cancer and, to that end, we expect to initiate a phase 1b/2 trial in patients before year end,” Exicure CEO David Giljohann said in a statement.
The phase 1b/2 trial will assess doses of AST-008 delivered intratumorally to patients with Merkel cell carcinoma, cutaneous squamous cell carcinoma, melanoma and squamous cell carcinoma of the head and neck. Exicure plans to combine AST-008 with a checkpoint inhibitor and have data on the phase 1b dose finding part of the trial late next year.