selectION, Inc.’s si-544 performed well in the first-in-human Phase 1b trial in atopic dermatitis (AD) patients.
si-544 is a selectivity-optimized peptide blocking the ion channel Kv1.3.
The completed Phase 1b trial was a multi-center, double-blind, placebo-controlled study in patients with mild to severe atopic dermatitis. The trial was designed to evaluate safety, tolerability, and efficacy signals of si-544.
si-544 was well tolerated up to the highest dose levels in the single ascending dose cohorts (s.c.) and in the multiple ascending dose cohorts (s.c.). Safety signals or dose limiting toxicities were not observed. Of note, limits of safety and tolerability were not reached at the highest doses administered in the study, therefore the maximum tolerated dose was not determined.
There were no serious adverse events and no dose reductions or temporary / permanent discontinuations of dosing due to adverse events.
Fully 75% of patients receiving drug experienced objective clinical improvement, and of these patients, 44% achieved clear or almost clear skin at the end of the monitoring period. The healing trend continued beyond dosing through the entire monitoring period, the study showed.
“The ion channel Kv1.3 controls the activation and proliferation of auto-reactive effector memory T-cells and has been regarded a key target in T-cell autoimmunity for decades,” says Andreas Klostermann, PhD, Chief Scientific Officer and co-founder of the Company, in a news release. “So far, it has not been possible to block this ion channel with sufficient selectivity.”
The initial analysis of safety and tolerability data from 27 patients in the single and multiple ascending dose cohorts confirmed that si-544 can be safely administered at dose levels sufficient to achieve virtually full Kv1.3 target engagement.
“It also demonstrates that our high-affinity Kv1.3-blocking peptide, si-544, has class-leading selectivity. To our knowledge, selectION is the first to achieve these important goals,” Klostermann says.
“Based on the results of this first clinical trial, we believe that si-544 has the potential to set a new benchmark for safety and tolerability in the treatment of T-cell autoimmunity,” adds Antonius Schuh, PhD, Chairman and CEO of selectION, Inc. “Study results indicate a clear initial efficacy signal. In addition, under continuous dosing no indication of immunosuppression has been observed. We are now planning to advance si-544 through clinical development and evaluate the compound in further autoimmune diseases.”
