Investigational Drug si-544 Improves PASI Scores in Patients with Psoriasis

New phase 1b data on si-544, a first-in-class Kv1.3 channel blocker, show positive findings on the drug’s efficacy and safety in patients with psoriasis vulgaris.1

These data were released on October 21, 2025, by SelectION, Inc., a clinical-stage biopharmaceutical company focused on developing treatments for T cell–mediated autoimmune diseases. The phase 1b proof-of-concept study of si-544, ar, in patients with psoriasis vulgaris was described as a milestone by the company.

“These results mark a significant milestone, as si-544 has, for the first time, clinically confirmed the long hypothesized and remarkable therapeutic potential of Kv1.3 in T cell autoimmunity,” Antonius Schuh, PhD, CEO of selectION, said in a statement.1 “This trial clinically validates Kv1.3 dependency as an ideal clinical entry point to disrupt the chronic activation of pathogenic, autoreactive T cells.”

The Kv1.3 voltage-gated potassium channel, known to be an established therapeutic target in autoimmune disorders. Autoreactive T cells, key drivers of autoimmune pathology, show a particular dependency on Kv1.3.2 The drug, by selectively and irreversibly blocking this channel, was designed to disrupt the activity of chronically activated pathogenic T cell clones while preserving normal immune function among patients.

This mechanism supports the notion that short treatment cycles of si-544 could yield durable, disease-modifying impacts across multiple autoimmune diseases such as psoriasis, atopic dermatitis, inflammatory bowel disease, rheumatoid arthritis, and even multiple sclerosis. The company described these phase 1b results as providing the first clinical confirmation of this hypothesis in psoriasis vulgaris, serving as a model for T cell–driven autoimmunity.

si-544 was described as having the potential to become a disease-modifying and safe option for treatment among patients with psoriasis, with disease reductions being both meaningful and durable. This phase 1b trial (NCT06191042) was designed as a randomized, double-blind, placebo-controlled analysis, with investigators conducting their research at 4 clinical sites in Germany.

Enrollment of patients involved a total of 45 adults living with mild-to-severe psoriasis vulgaris, with randomization in a 3:1 ratio. Subjects would receive si-544 or a placebo in the 2 arms of the analysis, and 2 subcutaneous injections were provided per week for 4 weeks. The participants were followed for an additional 12 weeks following the discontinuation of their treatment with si-544 or placebo.

The investigative team’s main objective of their analysis was to look into the safety and tolerability of si-544 through an assessment of adverse events, laboratory parameters, vital signs, and electrocardiograms (ECG). Secondary endpoints considered by the team included pharmacodynamics, pharmacokinetics, immunogenicity, and efficacy measures based on Physician’s Global Assessment (PGA), Psoriasis Area and Severity Index (PASI), and Body Surface Area (BSA) scores.

Overall, the investigators pointed to findings suggesting a 4-week treatment cycle led subjects on si-544 to demonstrate statistically significant improvements in their PASI scores (P< .05) as opposed to those in the placebo cohort. In terms of safety, si-544 was shown to be well-tolerated among participants, with no dose-limiting toxicities, treatment-related serious adverse events, or safety concerns being identified in the study.

In terms of onset and durability, the investigative team found clinical improvements to be evident as early as the 2-week mark, noting sustained disease stabilization as well as continued lesion healing throughout the 12-week post-treatment observation period of the analysis. Patients were also found to have retained full immunocompetence throughout the course of the research.

In all, the findings would indicate that si-544 attained its dual goals of safety and clinical efficacy among those with psoriasis vulgaris. These findings would support the medication’s potential as a disease-modifying therapy for psoriasis and other autoimmune conditions mediated by T cell dysfunction.

References

1. selectION Demonstrates Safety and Disease-Modifying Mechanism of Action of its Investigational Drug, si-544, in Phase 1b Proof-of-Concept Trial in Psoriasis, a T Cell-Mediated Autoimmune Disease. selectION, Inc. October 21, 2025. https://www.globenewswire.com/news-release/2025/10/21/3169961/0/en/selectION-Demonstrates-Safety-and-Disease-Modifying-Mechanism-of-Action-of-its-Investigational-Drug-si-544-in-Phase-1b-Proof-of-Concept-Trial-in-Psoriasis-a-T-Cell-Mediated-Autoimm.html.

2. Kundu-Raychaudhuri S, Chen YJ, Raychaudhuri SP, et al. Kv1.3 in psoriatic disease: PAP-1, a small molecule inhibitor of Kv1.3 is effective in the SCID mouse psoriasis--xenograft model. J Autoimmun. 2014 Dec;55:63-72. doi: 10.1016/j.jaut.2014.07.003. Epub 2014 Aug 28. PMID: 25175978; PMCID: PMC4398058.