Sonnet BioTherapeutics announces data in Phase 1 trial of SON-1010

Sonnet BioTherapeutics Holdings announced that pharmacokinetic profile simulation of SON-1010 dosing has been completed in its randomized, placebo-controlled Phase 1 clinical trial in healthy volunteers. Historically, the therapeutic application of cytokines has been limited by relatively short half-lives and off-target toxicities that are typically associated with peak plasma levels. SON-1010 is a proprietary version of recombinant human interleukin-12, configured using Sonnet’s Fully Human Albumin Binding technology, which has been shown to extend PK and to reduce peak drug levels for improving pharmacodynamic toxicity. The FHAB technology was designed to promote targeting to the tumor microenvironment, particularly when levels of Secreted Protein Acidic and Rich in Cysteine are elevated in the TME. Study SB102 is a single-ascending dose trial in healthy volunteers that was initiated in July, 2022 to address the safety, PK, and PD of SON-1010 in subjects without interference from prior chemotherapy. The Safety Review Committee has found no significant safety concerns to date and has approved advancing to each higher dose level. Typical dose-related increases were seen with SON-1010 using a validated electrochemi luminescence assay after subcutaneous administration. Drug levels peaked at about 11 hours with a geometric mean maximum concentration of 29, 68, and 125 pg/mL for the 50, 100, and 150 ng/kg dose groups, respectively. The mean elimination half-life after a 150 ng/kg dose of SON-1010 was 112 hours, compared to 12 hours for rhIL-12. Observed increases in IFNg were most pronounced and were dose-related, controlled, and prolonged. SON-1010 induced IFNg in all active-drug subjects, which peaked at 24 to 48 hours then returned to baseline after 2 weeks. The IFNg geomean Cmax was 398, 384, and 666 pg/mL after 50, 100, or 150 ng/kg of SON-1010, respectively, while the AUC over 48 hours was 6050, 10200, and 14600 h*pg/mL. Linear regression was used to predict the IFNg Cmax at higher doses, which remain well within the range of safety. Low amounts of IL-10 were induced in a dose-dependent manner, which could also be due to the increase in IFNg. There were small transient increases in IL-6, IL-8, and TNFalpha after dosing but no consistent pattern was seen with IL-1beta, IL-2, or IL-4 and there was no evidence of cytokine release syndrome . Safety was consistent with what has been reported previously; adverse events have generally been mild/moderate, transient in nature, and have all been tolerable.